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Chemical and Life Science Engineering Professor Michael “Pete” Peters, Ph.D., is investigating more efficient ways to manufacture biologic pharmaceuticals using a radial flow bioreactor he developed. With applications in vaccines and other personalized therapeutic treatments, biologics are versatile. Their genetic base can be manipulated to create a variety of effects from fighting infections by stimulating an immune response to weight loss by producing a specific hormone in the body. Ozempic, Wegovy and Victoza are some of the brand names for Glucagon-Like Peptide-1 (GLP-1) receptor agonists used to treat diabetes. These drugs mimic the GLP-1 peptide, a hormone naturally produced in the body that regulates appetite, hunger and blood sugar. “I have a lot of experience with helical peptides like GLP-1 from my work with COVID therapeutics,” says Peters. “When it was discovered that these biologic pharmaceuticals can help with weight loss, demand spiked. These drug types were designed for people with type-2 diabetes and those diabetic patients couldn’t get their GLP-1 treatments. We wanted to find a way for manufacturers to scale up production to meet demand, especially now that further study of GLP-1 has revealed other applications for the drug, like smoking cessation.” Continuous Manufacturing of Biologic Pharmaceuticals Pharmaceuticals come in two basic forms: small-molecule and biologic. Small-molecule medicines are synthetically produced via chemical reactions while biologics are produced from microorganisms. Both types of medications are traditionally produced in a batch process, where base materials are fed into a staged system that produces “batches” of the small-molecule or biologic medication. This process is similar to a chef baking a single cake. Once these materials are exhausted, the batch is complete and the entire system needs to be reset before the next batch begins. “ The batch process can be cumbersome,” says Peters. “Shutting the whole process down and starting it up costs time and money. And if you want a second batch, you have to go through the entire process again after sterilization. Scaling the manufacturing process up is another problem because doubling the system size doesn’t equate to doubling the product. In engineering, that’s called nonlinear phenomena.” Continuous manufacturing improves efficiency and scalability by creating a system where production is ongoing over time rather than staged. These manufacturing techniques can lead to “end-to-end” continuous manufacturing, which is ideal for producing high-demand biologic pharmaceuticals like Ozempic, Wegovy and Victoza. Virginia Commonwealth University’s Medicines for All Institute is also focused on these production innovations. Peters’ continuous manufacturing system for biologics is called a radial flow bioreactor. A disk containing the microorganisms used for production sits on a fixture with a tube coming up through the center of the disk. As the transport fluid comes up the tube, the laminar flow created by its exiting the tube spreads it evenly and continuously over the disk. The interaction between the transport medium coming up the tube and the microorganisms on the disk creates the biological pharmaceutical, which is then taken away by the flow of the transport medium for continuous collection. Flowing the transport medium liquid over a disc coated with biologic-producing microorganisms allows the radial flow bioreactor to continuously produce biologic pharmaceuticals. “There are many advantages to a radial flow bioreactor,” says Peters. “It takes minutes to switch out the disk with the biologic-producing microorganisms. While continuously producing your biologic pharmaceutical, a manufacturer could have another disk in an incubator. Once the microorganisms in the incubator have grown to completely cover the disk, flow of the transport medium liquid to the radial flow bioreactor is shut off. The disk is replaced and then the transport medium flow resumes. That’s minutes for a production changeover instead of the many hours it takes to reset a system in the batch flow process.” The Building Blocks of Biologic Pharmaceuticals Biologic pharmaceuticals are natural molecules created by genetically manipulating microorganisms, like bacteria or mammalian cells. The technology involves designing and inserting a DNA plasmid that carries genetic instructions to the cells. This genetic code is a nucleotide sequence used by the cell to create proteins capable of performing a diverse range of functions within the body. Like musical notes, each nucleotide represents specific genetic information. The arrangement of these sequences, like notes in a song, changes what the cell is instructed to do. In the same way notes can be arranged to create different musical compositions, nucleotide sequences can completely alter a cell’s behavior. Microorganisms transcribe the inserted DNA into a much smaller, mRNA coded molecule. Then the mRNA molecule has its nucleotide code translated into a chain of amino acids, forming a polypeptide that eventually folds into a protein that can act within the body. “One of the disadvantages of biologic design is the wide range of molecular conformations biological molecules can adopt,” says Peters. “Small-molecule medications, on the other hand, are typically more rigid, but difficult to design via first-principle engineering methods. A lot of my focus has been on helical peptides, like GLP-1, that are a programmable biologic pharmaceutical designed from first principles and have the stability of a small-molecule.” The stability Peters describes comes from the helical peptide’s structure, an alpha helix where the amino acid chain coils into a spiral that twists clockwise. Hydrogen bonds that occur between the peptide’s backbone creates a repeating pattern that pulls the helix tightly together to resist conformational changes. “It’s why we used it in our COVID therapeutic and makes it an excellent candidate for GLP-1 continuous production because of its relative stability,” says Peters. Programming The Cell Chemical and Life Science Engineering Assistant Professor Leah Spangler, Ph.D., is an expert at instructing cells to make specific things. Her material science background employs proteins to build or manipulate products not found in nature, like purifying rare-earth elements for use in electronics. “My lab’s function is to make proteins every day,” says Spangler. “The kind of proteins we make depends entirely on the project they are for. More specifically I use proteins to make things that don’t occur in nature. The reason proteins don’t build things like solar cells or the quantum dots used in LCD TVs is because nature is not going to evolve a solar cell or a display surface. Nature doesn’t know what either of those things are. However, proteins can be instructed to build these items, if we code them to.” Spangler is collaborating with Peters in the development of his radial flow bioreactor, specifically to engineer a microorganismal bacteria cell capable of continuously producing biologic pharmaceuticals. “We build proteins by leveraging bacteria to make them for us,” says Spangler. “It’s a well known technology. For this project, we’re hypothesizing that Escherichia coli (E. coli) can be modified to make GLP-1. Personally, I like working with E. coli because it’s a simple bacteria that has been thoroughly studied, so there’s lots of tools available for working with it compared to other cell types.” Development of the process and technique to use E. coli with the radial flow bioreactor is ongoing. “Working with Dr. Spangler has been a game changer for me,” says Peters. “She came to the College of Engineering with a background in protein engineering and an expertise with bacteria. Most of my work was in mammalian cells, so it’s been a great collaboration. We’ve been able to work together and develop this bioreactor to produce GLP-1.” Other Radial Flow Bioreactor Applications Similar to how the GLP-1 peptide has found applications beyond diabetes treatment, the radial flow bioreactor can also be used in different roles. Peters is currently exploring the reactor’s viability for harnessing solar energy. “One of the things we’ve done with the internal disc is to use it as a solar panel,” says Peters. “The disk can be a black body that absorbs light and gets warm. If you run water through the system, water also absorbs the radiation’s energy. The radial flow pattern automatically optimizes energy driving forces with fluid residence time. That makes for a very effective solar heating system. This heating system is a simple proof of concept. Our next step is to determine a method that harnesses solar radiation to create electricity in a continuous manner.” The radial flow bioreactor can also be implemented for environmental cleanup. With a disk tailored for water filtration, desalination or bioremediation, untreated water can be pushed through the system until it reaches a satisfactory level of purification. “The continuous bioreactor design is based on first principles of engineering that our students are learning through their undergraduate education,” says Peters. “The nonlinear scaling laws and performance predictions are fundamentally based. In this day of continued emphasis on empirical AI algorithms, the diminishing understanding of fundamental physics, chemistry, biology and mathematics that underlie engineering principles is a challenge. It’s important we not let first-principles and fundamental understanding be degraded from our educational mission, and projects like the radial flow bioreactor help students see these important fundamentals in action.”
3D-printed lung model helps researchers study aerosol deposition in the lungs
Treating respiratory diseases is challenging. Inhalable medicines depend on delivering particles to the right lung areas, which is complicated by factors like the drug, delivery method and patient variability, or even exposure to smoke or asbestos particles. University of Delaware researchers have developed an adaptable 3D lung model to address this issue by replicating realistic breathing maneuvers and offering personalized evaluation of aerosol therapeutics. “If it's something environmental and toxic that we're worried about, knowing how far and how deep in the lung it goes is important,” said Catherine Fromen, University of Delaware Centennial Associate Professor for Excellence in Research and Education in the Department of Chemical and Biomolecular Engineering. “If it's designing a better pharmaceutical drug for asthma or a respiratory disease, knowing exactly where the inhaled aerosol lands and how deep the medicine can penetrate will predict how well that works.”that can replicate realistic breathing maneuvers and offer personalized evaluation of aerosol therapeutics under various breathing conditions. Fromen and two UD alumni have submitted a patent application on the 3D lung model invention through UD’s Office of Economic Innovation and Partnerships (OEIP), the unit responsible for managing intellectual property at UD. In a paper published in the journal Device, Fromen and her team demonstrate how their new 3D lung model can advance understanding of how inhalable medications behave in the upper airways and deeper areas of the lung. This can provide a broader picture on how to predict the effectiveness of inhalable medications in models and computer simulations for different people or age groups. The researchers detail in the paper how they built the 3D structure and what they’ve learned so far. Valuable research tool The purpose of the lung is gas exchange. In practice, the lung is often approximated as the size of a tennis court that is exchanging oxygen and carbon dioxide with the bloodstream in our bodies. This is a huge surface area, and that function is critical — if your lungs go down, you're in trouble. Fromen described this branching lung architecture like a tree that starts with a trunk and branches out into smaller and smaller limbs, ranging in size from a few centimeters in the trachea to about 100 microns (roughly the combined width of two hairs on your head) in the lung’s farthest regions. These branches create a complex network that filters aerosols as they travel through the lung. Just as tree branches end in leaves, the lung’s branches culminate in delicate, leaf-like structures called alveoli, where gases are exchanged. “Those alveoli in the deeper airways make the surface area that provides this necessary gas exchange, so you don't want environmental things getting in there where they can damage these sensitive, finer structures,” said Fromen, who has a joint appointment in biomedical engineering. Mimicking the complex structure and function of the lung in a lab setting is inherently challenging. The UD-developed 3D lung model is unique in several ways. First, the model breathes in the same cyclic motion as an actual lung. That’s key, Fromen said. The model also contains lattice structures to represent the entire volume and surface area of a lung. These lattices, made possible through 3D printing, are a critical innovation, enabling precise design to mimic the lung's filtering processes without needing to recreate its full biological complexity. “There's nothing currently out there that has both of these features,” she explained. “This means that we can look at the entire dosage of an inhaled medicine. We can look at exposure over time, and we can capture what happens when you inhale the medication and where the medicine deposits, as well as what gets exhaled as you breathe.” The testing process Testing how far an aerosol or environmental particle travels inside the 3D lung model is a multi-step process. The exposure of the model to the aerosol only takes about five minutes, but the analysis is time-consuming. The researchers add fluorescent molecules to the solution being tested to track where the particles deposit inside the model’s 150 different parts. “We wash each part and rinse away everything that deposits. The fluorescence is just a molecule in the solution. When it deposits, we know the concentration of that, so, when we rinse it out, we can measure how much fluorescence was recovered,” Fromen said. This data allows them to create a heat map of where the aerosols deposit throughout the lung model’s airways, which then can be validated against benchmarked clinical data for where such aerosols would be expected to go in a human under similar conditions. The team’s current model matches a healthy person under sitting/breathing conditions for a single aerosol size, but Fromen’s team is working to ensure the model is versatile across a much broader range of conditions. “An asthma attack, exercise, cystic fibrosis, chronic obstructive pulmonary disorder (COPD) — all those things are going to really affect where aerosols deposit. We want to make sure our model can capture those differences,” Fromen said. The ability to examine disease features like airway narrowing or mucus buildup could lead to more personalized care, such as tailored medication doses or redesigned inhalers. Currently, inhaled medicines follow a one-size-fits-all approach, but the UD-developed model offers a tool to address these issues and understand why many inhaled medicines fail clinical trials.
MESOX, a spin-out from the pharmaceutics group at Aston Pharmacy School, develops drug carrier technology to improve medicine formulations The company won the Start-Up prize at the Medilink Midlands Awards 2024 The prize is awarded to a new company that shows a promising future. A spin-out company from Aston University’s pharmaceutics research group has won a medical technology and life sciences industry award. MESOX, which was founded by Aston University pharmaceutics lecturer Dr Ali Al-Khattawi, won the Medilink Midlands Start-Up Award, which is presented to a newly established company that shows a promising future. The Medilink Midlands Business Awards showcase the best collaborations between industry, academia and the NHS across the Midlands. This year’s ceremony was held at the Athena in Leicester on 9 May. The awards were established by Medilink Midlands, which provides specialist business support to boost the region’s economic output from the life sciences industry. Working alongside the Midlands Engine and other strategic alliances, it helps stimulate additional and value-added growth of the Midlands as a prosperous community for life sciences. With in-depth expertise in particle engineering for drug delivery and pharmaceutical spray drying, MESOX uses IP-protected carriers to improve the bioavailability and efficacy of pharmaceuticals, partnering with pharmaceutical and biotechnology companies to bring challenging therapeutics to market. In its citation, Medilink Midlands described MESOX as “transforming pharmaceutical formulation with its game-changing carrier technologies.” As a winner of a Medilink Midlands award, MESOX will now be entered into the UK National Awards, the ceremony of which takes place on 11 July 2024 in London. Dr Al-Khattawi said: “We are delighted to have won this prestigious award, which highlights the outstanding research and development work being done by the MESOX team and the immense potential of our company to transform the medicine formulation development landscape. Through collaboration with other pharmaceutical companies, clinicians, academic researchers, and by engaging directly with patients to understand their needs, we aim to innovate and advance drug delivery science into life-saving therapeutics. “At MESOX, our ambition is to be a global, research-based pharmaceutical company rooted in the Midlands, dedicated to developing life-saving therapeutics at speed and resource-efficiency. Our ultimate goal is to enable healthier lives for patients worldwide and ensure better global access to essential medicines.”
Aston University pharmaceutical spin-out company shortlisted in life sciences industry awards
MESOX is a spin-out from the pharmaceutics group at Aston Pharmacy School The company partners with pharmaceutical and biotechnology companies to bring challenging therapeutics to market It has been shortlisted in the Medilink Midlands Awards 2024. A spin-out company from Aston University’s pharmaceutics research group has been shortlisted for a life sciences industry award. The Medilink Midlands Awards aim to showcase the very best collaborations between industry, academia and the NHS across the Midlands. The company, MESOX, founded by Dr Ali Al-Khattawi, a lecturer in pharmaceutics at Aston Pharmacy School, is competing in the Start-Up category for newly established companies that show a promising future. With in-depth expertise in particle engineering for drug delivery and pharmaceutical spray drying, MESOX uses IP-protected carriers to improve the bioavailability and efficacy of pharmaceuticals, partnering with pharmaceutical and biotechnology companies to bring challenging therapeutics to market. Medilink Midlands provides specialist business support to boost the region’s economic output from the life sciences industry. Working alongside the Midlands Engine and other strategic alliances, it helps stimulate additional and value-added growth of the Midlands as a prosperous community for life sciences. The awards winners will be announced at a ceremony taking place on Thursday 9 May at the Athena in Leicester. To celebrate Medilink Midlands’ 20th year anniversary of delivering business support, one finalist will be announced as the 2024 ‘Winner of all Winners’ and presented with a £5,000 prize for innovation development. Dr Ali Al-Khattawi, founder and CEO of MESOX, said: “We are excited to be nominated as a finalist for this award, which is a testament to the innovative research at Aston University that has led to MESOX and a great way to recognise the efforts of our team. “MESOX is expediting the development of life-saving therapeutics through cutting-edge carrier technologies. Our vision is to be a leading research-based pharmaceutical company in the Midlands one day and we hope this opportunity brings us a step closer to this goal.” Luke Southan, technology transfer manager at Aston University, said: “Aston University’s School of Pharmacy has always been a hotbed of innovation and entrepreneurship. This is most often seen through our many students who end up running their own independent pharmacy stores, but it is also the school that has created the most Aston spinouts. “MESOX is the latest example of this, and it is a company that is on track to be generating significant revenue and region impact over the next five years. This award nomination evidences the potential the company has to offer.”
New Aston University spin-out company will develop novel ways to treat non-healing wounds
EVolution Therapeutics (EVo) has been founded on the work of Professor Andrew Devitt into the causes of inflammatory disease A failure to control inflammation in the body, usually a natural defence mechanism, can cause chronic inflammation, such as non-healing wounds Non-healing wounds cost the NHS £5.6bn annually, so there is a vital need for new treatments. Aston University’s Professor Andrew Devitt, Dr Ivana Milic and Dr James Gavin have launched a new spin-out company to develop revolutionary treatments to treat chronic inflammation in patients. One of the most common inflammatory conditions is non-healing wounds, such as diabetic foot ulcers, which cost the NHS £5.6bn annually, the same cost as managing obesity. Such wounds are generally just dressed, but clinicians say there is a vital need for active wound treatments, rather than passive management. The spin-out, Evolution Therapeutics (EVo), will aim to create these vital active treatments. Inflammation in the human body helps to fight infection and repair damage following injury and occurs when the immune system floods the area with immune cells. Normally, this inflammation subsides as the damage heals, with the immune system signalling to the immune cells to leave. However, in some cases, the usual healing mechanism is not triggered and the inflammatory response is not turned off, leading to chronic inflammation and so-called inflammatory diseases. EVo is based on Professor Devitt’s work on dying cells in the body, known as apoptotic cells, and how they contribute to health. Dying cells release small, membrane-enclosed fragments called extracellular vesicles (EVs), which alert the immune system to the death of cells, and then trigger the body’s natural repair mechanism and remove the dead cells. It is estimated that 1m cells die every second. Professor Devitt and his team have identified the molecules within the EVs which control the healing process and are engineering new EVs loaded with novel healing enzymes, to drive the body’s repair responses to actively heal wounds. Much of the research has been funded by the Biotechnology and Biological Sciences Research Council (BBSRC) with additional support from the Dunhill Medical Trust. Professor Devitt, Dr Milic and Dr Gavin received Innovation-to-Commercialisation of University Research (ICURe) follow-on funding of £284,000 to develop the vesicle-based therapy with EVo. Most recently, in December 2023, Professor Devitt and Dr Milic were awarded £585,000 from the BBSRC Super Follow-on-Fund to develop engineered cells as a source of membrane vesicles carrying inflammation controlling cargo. The team, together with Professor Paul Topham, also received funding from the National Engineering Biology Programme (£237,000) to support polymer delivery systems for vesicles. EVo is one of the 12 projects being supported by SPARK The Midlands, a network which aims to bridge the gap between medical research discoveries of novel therapeutics, medical devices and diagnostics, and real-world clinical use. SPARK The Midlands is hosted at Aston University, supported by the West Midlands Health Tech Innovation Accelerator (WMHTIA), and was launched at an event on 31 January 2024. Professor Devitt, EVo chief technical officer, said: “Inflammation is the major driver of almost all disease with a huge contribution to those unwelcome consequences of ageing. We are now at a most exciting time in our science where we can harness all the learning from our research to develop targeted and active therapies for these chronic inflammatory conditions.” Dr Gavin, EVo CEO, said: “The chronic inflammation that results in non-healing wounds are a huge health burden to individuals affecting quality of life as we age but also to the economy. Our approach at EVo is to target the burden of non-healing wounds directly to provide completely novel approaches to wound care treatment. By developing a therapy which actively accelerates wound healing, we hope to drastically improve quality of life for patients, whilst reducing the high cost attached to long term treatment for healthcare systems worldwide.”
Below is a statement from Eric Kmiec, Ph.D., founder and executive director, ChristinaCare Gene Editing Institute, regarding the expected approval by the Food and Drug Administration of exa-cel (Casgevy), the CRISPR-driven treatment for sickle cell disease and betta thalassemia. If you wish to interview Dr. Kmiec, please contact Mak Sisson, Makenzie.sisson@christinacare.org,302-623-5306 or Anna Chen, achen@burness.com, 215-262-7670. “As scientists, the fact that we have arrived at a potential curative treatment for sickle cell disease in a relatively brief period is a testament to the power of resolute researchers in this field who have never stopped. And the FDA’s expected approval comes with many firsts. For the first time we have what appears to be a safe and curative treatment for one of the most painful diseases that cuts life short. And it is remarkable that finally we are focusing on the Black population first, who are most affected by this disease. This priority is long, long overdue. The challenge, however, is the very people we want to help may not be able to get access to or afford the million-dollar treatment and the length of time it will take to be treated — weeks and weeks in the hospital. The numbers of people who can be treated are limited. We must work with the health care industry and pharmaceutical companies who will market produce and deliver the treatments to make sure that all people can get access. What can they do to make treatments more affordable and more available? What can they do to support continued research to assess the long-term effects this treatment may have? And how can we make this easier to deliver? As important as it is to have developed this new treatment, right now we must do our best to communicate well to the public what new findings like this mean. Take the time to explain it all. It cannot be oversold. We must make the communication about this first CRISPR-driven treatment as important as the science itself.” Eric B. Kmiec, Ph.D., is the founder and executive director of the Gene Editing Institute at ChristianaCare. He is also co-founder and chief scientific officer of CorriXR Therapeutics. Widely recognized for his pioneering work in the fields of molecular medicine and gene editing, Dr. Kmiec has developed CRISPR based genetic therapies for Sickle Cell Disease and Non-Small Cell Lung Cancer. He is Editor-in-Chief of the journal, Gene and Genome Editing.
For the third time, Modern Healthcare has selected ChristianaCare President and CEO Janice E. Nevin, M.D., MPH, for its Top 25 Women Leaders list. The editors highlighted the bold strategic enterprise plan that Dr. Nevin has set for ChristianaCare, which focuses on vital areas, including addressing care disparities, effectively supporting employees, simplifying access to health services and accelerating transformation and growth. They noted a number of specific initiatives related to the strategic plan, such as the rollout of Moxi cobots, which have improved the workflows for nurses and patient care technicians by handling low-value tasks like deliveries. Modern Healthcare also cited that this past year ChristianaCare spun off its first-ever private, commercial startup company, CorriXR Therapeutics, which is using CRISPR gene editing technology to develop cancer therapeutics, starting with lung cancer. “Dr. Nevin has set ChristianaCare on a bold path forward,” said Nicholas M. Marsini, Jr., chair of the ChristianaCare Health System Board of Directors. “She leads the health system guided by our values of love and excellence, addressing difficult problems head on with courage and empathy. As ChristianaCare sets a model in so many ways for other health care organizations across the country, Dr. Nevin’s local and national impact make her most deserving of this recognition.” Dr. Nevin has been president and CEO of ChristianaCare since 2014. Under her leadership ChristianaCare has become one of America’s 50 Best Hospitals, according to Healthgrades. The system has also been lauded as one of the nation’s best large employers overall and specifically for inclusion and diversity. Modern Healthcare’s list of the Top 25 Women Leaders acknowledges and honors women executives from all sectors of the health care industry for their contributions to care delivery improvement, health equity, policy and gender equity in leadership. “They are innovators and team-builders advancing their organizations. They are mentoring co-workers while inspiring others to pursue careers in the industry,” said Mary Ellen Podmolik, editor-in-chief of Modern Healthcare. “And externally, they are forging coalitions to improve access to care for all patients. The women we’ve selected this year, from hundreds of nominations, are leading important advancements in the nation’s healthcare system.” This year’s honorees are profiled in the Feb. 20 issue of Modern Healthcare magazine and online at www.modernhealthcare.com/topwomenexecs.
ChristianaCare Spins Out CorriXR Therapeutics, New Gene Editing Start-Up
Commercial biotechnology venture will harness the power of gene editing to revolutionize patient care with faster, more accurate diagnoses ChristianaCare today announced it has spun out its first commercial biotechnology private start-up company, named CorriXR Therapeutics. CorriXR Therapeutics (pronounced Cor-ix-er; from Galician meaning to correct or edit) will use CRISPR gene editing technology to develop new, clinically relevant oncologic therapeutics in areas of unmet medical need, starting with squamous cell carcinoma of the lung. Its close relationship with ChristianaCare and the ChristianaCare Gene Editing Institute uniquely positions it to research and develop innovative, patient-centered therapies. The new start-up company has been boosted with $5 million in seed financing from ChristianaCare and Brookhaven Bio. “We are excited to spin out CorriXR Therapeutics, which has an enormous opportunity to use the incredible power of gene editing to revolutionize patient care by delivering faster and more accurate diagnoses, targeting treatments and preventing genetic disorders,” said Janice Nevin, M.D., MPH, ChristianaCare president and CEO. The company has developed unique CRISPR/Cas biomolecular tools that disable the genome of a tumor cell but not the genome of a healthy cell, which enables target selectivity. CorriXR Therapeutics will license technology from the Gene Editing Institute and work closely with its scientific researchers and clinical oncologists at the Helen F. Graham Cancer Center & Research Institute. The Gene Editing Institute’s integrated bench-to-bedside approach connects leading-edge science to patient care. “CorriXR Therapeutics is the next phase of the Gene Editing Institute’s evolution and impact as an incubator for groundbreaking technology in a patient-first approach to research,” said Eric Kmiec, Ph.D., chief executive officer of CorriXR Therapeutics. “The novel way we are using CRISPR-directed gene editing technology in solid tumors, beginning with a hard-to-treat form of lung cancer, has enormous promise as a treatment option to improve the lives of people with life-threatening disease.” The CorriXR Therapeutics team includes experienced biotechnology executives and world-renowned scientists and clinicians. The executive team is led by Eric Kmiec, Ph.D., chief executive officer, and Brian Longstreet, chief operating officer. Kmiec is also the executive director and chief scientific officer of ChristianaCare’s Gene Editing Institute. He is widely recognized for his pioneering work in the fields of molecular medicine and gene editing, having discovered many of the molecular activities that regulate the efficiency of human gene editing. Longstreet, a graduate of the University of Pennsylvania’s Wharton School of Business, is a seasoned pharma and biotechnology industry veteran with over 30 years’ experience, beginning at Schering-Plough and then Merck & Co. Recently, he has helped to build start-up biotechnology companies. Earlier this year, ChristianaCare restructured its Gene Editing Institute into a wholly owned subsidiary, which positions it to advance research to develop therapies using CRISPR gene editing technology and to fast-track discoveries for commercial application. The new structure also enables it to expand its educational outreach using its CRISPR in a Box™ educational toolkit and to develop its analytic software program, DECODR™. The Gene Editing Institute originated in ChristianaCare’s Helen F. Graham Cancer Center & Research Institute in 2015.
ChristianaCare and The Wistar Institute advance partnership with new cancer research strategies
ChristianaCare’s Helen F. Graham Cancer Center & Research Institute is advancing its historic partnership with the Ellen and Ronald Caplan Cancer Center of The Wistar Institute in Philadelphia with three new research projects under way. The new research projects consist of a population health study targeting triple negative breast cancer. Other projects focus on a new therapeutic target for epithelial ovarian cancer, the most lethal gynecologic cancer in the developed world, and the development of “mini organs” derived from stem cells. Targeting triple negative breast cancer Delaware has one of the highest incidence rates of triple-negative breast cancer in the United States. This highly aggressive cancer has few treatment options, because the cells test negative for three known treatment targets – estrogen, progesterone and HER2 protein receptors. Working with patient data from the Graham Cancer Center, researchers are investigating potential contributing factors such as diet, alcohol use and genetic variants among women, and the effects of these on cancer metabolism. The team will also examine spatial relationships between cancer “hot spots”—geographic areas with a higher-than-expected prevalence—and modifiable risk factors. Key resources for the study are blood and tissue samples from the Graham Cancer Center’s Tissue Procurement Center and its statewide High-Risk Family Cancer Registry. The research team will be led by Director of Population Health Research at ChristianaCare Scott Siegel, Ph.D., and Lead Research Scientist Jennifer Sims Mourtada, Ph.D., at the Graham Cancer Center’s Cawley Center for Translational Cancer Research (CTCR). They will join Zachary Schug, Ph.D., at Wistar’s Molecular and Cellular Oncogenesis Program. Researching novel therapy for ovarian cancer The latest study supported by the Graham Cancer Center’s Tissue Procurement Program targets KAT6A expression as a novel therapy for ovarian cancer caused by a specific genetic mutation, called PP2R1A. Epithelial ovarian cancer is the most common form of ovarian cancer and the leading cause of gynecologic cancer deaths in the United States. Chemoresistance to currently available platinum-based drugs like cisplatin represents a major treatment challenge, as more than 50 percent of affected women ultimately relapse and die from this disease. Wistar’s Rugang Zhang, Ph.D., leader of the Immunology, Microenvironment and Metastases Program, is focused on developing novel therapeutics for subtypes of ovarian cancer that currently have no effective therapies and on improving the current standard of care. Dr. Zhang’s previous work suggests that KAT6A signaling plays a critical role in ovarian cancer progression. Targeting this signaling pathway could be an effective strategy for treating ovarian cancer. Working with Dr. Zhang on this project are Graham Cancer Center gynecologic oncologists Mark Cadungog, M.D., director of Robotic Surgery, and Sudeshna Chatterjee-Paer, M.D., and Cawley CTCR’s Stephanie Jean, M.D., director of Gynecologic Oncology Research. Also collaborating with the team is Wistar’s Alessandro Gardini, Ph.D., assistant professor in the Gene Expression & Regulation Program. ‘Mini organs’ offer hope for therapeutics Dr. Sims-Mourtada at the Cawley CTCR will lead a new program to culture organ-specific tissue from stem cells that could change the way diseases are studied and treated. These so called “mini organs” or “organoids” are three-dimensional tissue cultures grown in the lab that replicate the complexity and functions of a specific tissue or organ found in the body. Organoids offer scientists a better model for how drugs and other therapeutics might interact with a patient’s particular type of tumor, opening new avenues for precision medicine. “The ability to grow each patient’s tumor in a three-dimensional organoid along with our capability to create patient-derived xenograft or animal models as part of our PDX core, will allow us to fully capture the effects of genetic as well as gene altering behavioral and environmental influences that are lacking in current research models,” said Dr. Sims-Mourtada. “Our collaboration with Wistar to build these programs raises our clinical platform to the next level for studying new cancer biomarkers and treatments.” Advancing a Pioneering Partnership The Graham Cancer Center made history when it signed a first-of-its-kind agreement in 2011 with The Wistar Institute, pairing a National Cancer Institute, NCI-designated basic research institution with a community cancer center that is also an NCI Community Oncology Research Program (NCORP). “Our partnership with Wistar has attracted national recognition as a model of collaboration that leverages cutting-edge research to benefit cancer prevention and therapy statewide,” says Nicholas J. Petrelli, M.D., Bank of America endowed medical director of ChristianaCare’s Helen F. Graham Cancer Center and Research Institute. “With Wistar, our productive collaborations over the last decade continue to drive discovery research toward clinical trials to benefit patients here at the Graham Cancer Center and in communities everywhere.” “The Graham Center has been an ideal partner in our mission,” said Dario C. Altieri, M.D., Wistar president and CEO and director of the Ellen and Ronald Caplan Cancer Center. “Our scientists at Wistar have access to clinically-annotated primary patient specimens of the highest quality. As the majority of patients at the Graham Cancer Center are treatment naïve, this collaboration affords an opportunity to conduct unique, high impact mechanistic and correlative studies that will ultimately advance important scientific discoveries that hopefully will lead to better cancer therapies.”
New process to identify existing drugs for potential COVID-19 treatments
In late January, as the world watched the growing COVID-19 epidemic with increasing unease, a Michigan State University laboratory, which specializes in the use of artificial intelligence and big data to discover therapeutics for cancers, switched gears to face the coming challenge. The Chen Lab, led by Bin Chen, assistant professor in the Department of Pediatrics and Human Development, and the Department of Pharmacology and Toxicology, put its expertise to work. They developed a computational process for identifying existing drugs that may be repurposed to fight the SARS-CoV-2 virus without needing access to the virus itself. When a virus infects a human cell, it hijacks the reproductive capabilities to replicate and survive. In doing so, the virus interferes in the activity of the host cell’s genes. Each virus leaves a unique imprint on the cell at a certain point of infection — known scientifically as a gene expression signature — that is detectable by modern laboratory technologies. “We wanted to find a drug that could block the gene expression change in the host cells, hoping to mitigate disease progression and alleviate symptoms,” Chen said. Meanwhile, scientists worldwide knew almost nothing about the new virus and access to live virus samples was limited at best, he said. Based on a number of publicly-available datasets, Chen and his team surmised that other members of the coronavirus family — SARS and MERS — could approximate the gene expression signature of the new virus. Using the lab’s existing library of FDA-approved or clinically-investigated drugs and an established drug prediction pipeline, the team examined thousands of potential drug candidates through a complex methodology of scoring, rating and ranking potential candidates against known gene expression signatures. “Fortunately, we found a number of drugs that could be effective,” Chen said. “But we needed to do more. We needed biological validation.” In collaboration with researchers at the University of Texas Medical Branch, Chen tested the top-rated drug candidates on kidney cells derived from an African green monkey, a common cell line used in toxicology and virology research. The cells were first treated with the drug and later infected by the new SARS-CoV-2 virus. “We sent 10 drugs to them and it turns out that four drugs were able to prevent the virus-induced effects,” Chen said. “Unfortunately, the drugs, which are used to treat cancer, are also rather toxic. But the concept worked. Our process worked. We can now find more potential drugs to reverse the impacts of the virus and keep those less toxic drugs for further investigation.” “I’m very appreciative of how open the scientific community has been,” Chen said. “We knew very little at the beginning, but scientists have been making their work available to the community so that we can act.” Researchers in South Korea tested 35 FDA-approved drugs for antiviral efficacy against actual SARS-CoV-2 samples. Fourteen positive drugs overlapped with Chen Lab’s screening library and were also ranked highly by the methodology. This data also externally validated the predictive ability of Chen’s discovery process. “We are striving to use the best science possible to help patients,” Chen said. He intends to make their work available immediately. “We need to release this data to the public. Other laboratories across the world may be able to learn from our work,” Chen said. “They can select new compounds to investigate. There are so many drugs to screen. We alone cannot test them all.” If you are a journalist looking to learn more about Dr. Chen and his ongoing work to treat COVIS-19 - then let us help. Dr. Bin Chen is available to speak with media regarding his work - simply click on his icon to arrange an interview today.
