James Dahlman

Assistant Professor, Biomedical Engineering Georgia Tech College of Engineering

  • Atlanta GA

James Dahlman uses molecular biology to rationally design the genetic drugs he delivers.

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Gene therapy and the next frontier of medicine

Genetic testing today is mainstream, marketing to consumers who want to know where in Europe they came from or what types of hereditary diseases they could develop. For around $200 you can trace your family tree to learn your origins or identify genetic abnormalities that could signal disease. James Dahlman, assistant professor in the College of Engineering’s biomedical engineering department, specializes in genetics and believes these genotyping services can be helpful, as long as they are used responsibly. “If you’re going to start making medical predictions, you have to be careful,” said Dahlman. “Most people are not equipped to interpret statistics correctly, which can lead to negative predicting and ethical dilemmas. In a few years, genetic counselors will be in high demand so folks can make better decisions about their health.” Dahlman is fascinated by genetics, citing gene therapy as the most interesting field in the world. And it’s a field that he is revolutionizing through his research. Gene therapy is an experimental technique that uses genes to treat or prevent diseases, including hemophilia, Parkinson’s, cancer and HIV. It can help manage a number of diseases by leveraging genes instead of drugs or surgery. Although gene therapy shows promise, there are still risks involved, including unwanted immune system reactions or the risk of the wrong cells being targeted. That’s where Dahlman’s research comes in. Dahlman’s lab focuses on drug delivery vehicles, which are nanoparticles. The nanoparticle delivers gene therapies to the right place in the body to fight disease. It’s critical that the gene therapies only target the unhealthy cells to avoid damaging healthy ones. Dahlman is laser focused on ensuring the nanoparticles know what paths to take to reach the correct organ to start the healing process. “The issue with genetically-engineered drugs is that they don’t work unless they get to the right cell in the body,” said Dahlman. “You can have the world’s best genetic drug that's going to fix a tumor or eradicate plaque, but it’s not going to be effective unless it travels to the right organ. In my lab, we design different nanoparticles to deliver the genetically-engineered drugs to the correct location.” The field of genetic therapy is fascinating – and if you are a journalist looking to cover this topic or have questions for upcoming stories – let our experts help. James Dahlman is an Assistant Professor in the Georgia Tech BME Department. He is an expert in the area of biomedical engineering and uses molecular biology to rationally design the genetic drugs he delivers. This research is redefining the field of genetic therapy. Dr. Dahlman is available to speak with media – simply click on his icon to arrange an interview.

James Dahlman

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Biography

James Dahlman is an Assistant Professor in the Georgia Tech BME Department. He studied RNA design and gene editing as a post-doc with Feng Zhang at the Broad Institute, and received his PhD from MIT and Harvard Medical School in 2014, where he studied RNA delivery with Robert Langer and Daniel Anderson.

The Lab for Precision Therapies at Georgia Tech, also called the 'Dahlman Lab', works at the interface of drug delivery, nanotechnology, genomics, and gene editing. James has designed nanoparticles that deliver RNAs to the lung and heart; these nanoparticles have been used by over ten labs across the US to date. He has also developed targeted in vivo combination therapies; nanoparticles deliver multiple therapeutic RNAs at once, in order to manipulate several nodes on a single disease pathway. More recently, he developed a method to quantify the targeting, biodistribution, and pharmacokinetics of dozens to hundreds of distinct nanoparticles at once directly in vivo.

Finally, James uses molecular biology to rationally design the genetic drugs he delivers. He recently reported 'dead' guide RNAs; these engineered RNAs can be used to simultaneously up- and down-regulate different genes in a single cell using Cas9.

James has won the NSF, NDSEG, NIH OxCam, Whitaker Graduate, and LSRF Fellowships, the Weintraub Graduate Thesis Award, and was recently named a Bayer Young Investigator and Parkinson's Disease Foundation Young Investigator. He has had significant help along the way. Besides having great scientific advisors, James has been lucky to mentor excellent students, including two that were finalists for the Rhodes Scholarship.

Areas of Expertise

Vascular and Immunoengineering
DNA Barcoded Nanoparticles
Drug Delivery
CRISPR
Gene Editing
Cas9
RNA Therapies
Big Data / Nanotechnology

Selected Accomplishments

Young Innovator

2019
Cellular and Molecular Bioengineering

Emerging Investigator

2018
Named an emerging investigator in chemistry / materials science by the Journal of Materials Chemistry B

Education

MIT

Ph.D.

Medical Engineering

2014

Wright State University

B.S.

Biomedical Engineering

2009

Selected Media Appearances

DNA Data Storage Is Closer Than You Think

Scientific American  online

2019-07-01

Every minute in 2018, Google conducted 3.88 million searches, and people watched 4.33 million videos on YouTube, sent 159,362,760 e-mails, tweeted 473,000 times and posted 49,000 photos on Instagram, according to software company Domo. By 2020 an estimated 1.7 megabytes of data will be created per second per person globally, which translates to about 418 zettabytes in a single year (418 billion one-terabyte hard drive’s worth of information), assuming a world population of 7.8 billion. The magnetic or optical data-storage systems that currently hold this volume of 0s and 1s typically cannot last for more than a century, if that. Further, running data centers takes huge amounts of energy. In short, we are about to have a serious data-storage problem that will only become more severe over time.

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Red Glow Helps Identify Nanoparticles for Delivering RNA Therapies

Georgia Tech News Center  online

2018-10-01

A new screening process could dramatically accelerate the identification of nanoparticles suitable for delivering therapeutic RNA into living cells. The technique would allow researchers to screen hundreds of nanoparticles at a time, identifying the organs in which they accumulate – and verifying that they can successfully deliver an RNA cargo into living cells.

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MIT Technology Review Applauds Georgia Tech’s Dahlman in ‘35 Innovators Under 35’

Georgia Institute of Technology  online

2018-07-02

When a recognition makes your name fit comfortably into the same sentence with Facebook’s “Mark Zuckerberg” or Google co-founder “Larry Page,” you know it’s something special. A shout-out in the MIT Technology Review’s annual roster of “35 Innovators Under 35” did just that for Georgia Tech biomedical researcher James Dahlman.

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Patents

Novel crispr enzymes and systems

US20190233814A1

2019-08-21

The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA or RNA-targeting systems comprising a novel DNA or RNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.

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Conjugated lipomers and uses thereof

US20190167795A1

2019-06-06

wherein R3 and R4 are as defined herein. Also provided are compositions comprising the inventive conjugated lipomers, and methods of preparation and use.

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Selected Articles

Ligand Conjugated Multimeric siRNAs Enable Enhanced Uptake and Multiplexed Gene Silencing

Nucleic Acid Therapeutics

Jonathan M. Brown, James E. Dahlman, Kristin K. Neuman, Carla A.H. Prata, Monika C. Krampert, Philipp M. Hadwiger, and Hans-Peter Vornlocher

2019

Small interfering RNAs (siRNAs) conjugated to N-acetylgalactosamine (GalNAc) ligands have been used to treat disease in patients. However, conjugates with other ligands deliver siRNA less efficiently, limiting the development of new targeted therapies. Most approaches to enhancing the potency of such conjugates have concentrated on increasing ligand effectiveness and/or the chemical stability of the siRNA drug. One complementary and unexplored alternative is to increase the number of siRNAs delivered per ligand. An ideal system would be a single chemical entity capable of delivering multiple copies of an oligonucleotide drug and/or several such drugs simultaneously. Here we report that siRNAs can be stably linked together under neutral aqueous conditions to form chemically defined siRNA “multimers,” and that these multimers can be delivered in vivo by a GalNAc ligand. Conjugates containing multiple copies of the same siRNA showed enhanced activity per unit of ligand, whereas siRNAs targeting different genes linked to a single ligand facilitated multigene silencing in vivo; this is the first demonstration of silencing several genes simultaneously in vivo using ligand-directed multimeric siRNA. Multimeric oligonucleotides represent a powerful and practical new approach to improve intracellular conjugate delivery.

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BOLA (BolA Family Member 3) Deficiency Controls Endothelial Metabolism and Glycine Homeostasis in Pulmonary Hypertension

Circulation

Qiujun Yu, Yi-Yin Tai, Ying Tang, Jingsi Zhao, Vinny Negi, Miranda K Culley, Jyotsna Pilli, Wei Sun, Karin Brugger, Johannes Mayr, Rajeev Saggar, Rajan Saggar, W Dean Wallace, David J Ross, Aaron B Waxman, Stacy G Wendell, Steven J Mullett, John Sembrat, Mauricio Rojas, Omar F Khan, James E Dahlman, Masataka Sugahara, Nobuyuki Kagiyama, Taijyu Satoh, Manling Zhang, Ning Feng, John Gorcsan III, Sara O Vargas, Kathleen J Haley, Rahul Kumar, Brian B Graham, Robert Langer, Daniel G Anderson, Bing Wang, Sruti Shiva, Thomas Bertero, Stephen Y Chan

2019

Deficiencies of iron-sulfur (Fe-S) clusters, metal complexes that control redox state and mitochondrial metabolism, have been linked to pulmonary hypertension (PH), a deadly vascular disease with poorly defined molecular origins. BOLA3 (BolA Family Member 3) regulates Fe-S biogenesis, and mutations in BOLA3 result in multiple mitochondrial dysfunction syndrome, a fatal disorder associated with PH. The mechanistic role of BOLA3 in PH remains undefined.

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Nanoparticles Containing Oxidized Cholesterol Deliver mRNA to the Liver Microenvironment at Clinically Relevant Doses

Advanced Materials

Kalina Paunovska, Alejandro J Da Silva Sanchez, Cory D Sago, Zubao Gan, Melissa P Lokugamage, Fatima Z Islam, Sujay Kalathoor, Brandon R Krupczak, James E Dahlman

2019

Using mRNA to produce therapeutic proteins is a promising approach to treat genetic diseases. However, systemically delivering mRNA to cell types besides hepatocytes remains challenging. Fast identification of nanoparticle delivery (FIND) is a DNA barcode‐based system designed to measure how over 100 lipid nanoparticles (LNPs) deliver mRNA that functions in the cytoplasm of target cells in a single mouse. By using FIND to quantify how 75 chemically distinct LNPs delivered mRNA to 28 cell types in vivo, it is found that an LNP formulated with oxidized cholesterol and no targeting ligand delivers Cre mRNA, which edits DNA in hepatic endothelial cells and Kupffer cells at 0.05 mg kg−1. Notably, the LNP targets liver microenvironmental cells fivefold more potently than hepatocytes. The structure of the oxidized cholesterols added to the LNP is systematically varied to show that the position of the oxidative modification may be important; cholesterols modified on the hydrocarbon tail associated with sterol ring D tend to outperform cholesterols modified on sterol ring B. These data suggest that LNPs formulated with modified cholesterols can deliver gene‐editing mRNA to the liver microenvironment at clinically relevant doses.

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