Improving RNA and gene editing therapies by testing thousands of nanoparticles in vivo using DNA barcodes
Event details
| Date | 15.04.2019 |
| Hour | 09:00 › 10:00 |
| Speaker | Prof. James E. Dahlman, PhD, Dept. of Biomedical Engineering, Georgia Institute of Technology, Emory School of Medicine, Atlanta, GA (USA) |
| Location | |
| Category | Conferences - Seminars |
Abstract:
RNA-based drugs can turn on (or off) any gene in the genome. However, whether the drug is made out of siRNA, mRNA, lncRNA, or CRISPR, all RNA therapies are limited by one problem: drug delivery. Chemists can design thousands of distinct nanoparticles to deliver RNA. However, after nanoparticles are synthesized, they are tested in in vitro systems which do not have a liver, kidney, spleen, immune system, pulsatile blood flow, or other factors that affect nanoparticle delivery in vivo. To test thousands of nanoparticles in vivo, we designed a series of increasingly advanced DNA barcoding platforms. Our goal is to quantify how up to 500 nanoparticles functionally deliver mRNA or siRNA into up to 40 cell types, all in a single mouse. Since 2016, we have (i) generated nearly 200,000 in vivo drug delivery datapoints, (ii) developed a customized bioinformatics pipeline to iteratively ‘evolve’ nanoparticles that target new cell types in the spleen, liver, and bone marrow, (iii) identified nanoparticles that facilitate Cas9 gene editing outside the liver, (iv) characterized how internal metabolic signaling alters nanoparticle delivery in vivo, and (v) used in vivo synthetic biology to control therapeutic Cas9 editing in new tissues. Our data demonstrate that barcoded LNPs can elucidate fundamental questions about in vivo nanoparticle delivery, and identify nanoparticles for in vivo gene therapies.
Bio:
James Dahlman, PhD, is Assistant Professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech University. He is a member of the Discovery and Developmental Therapeutics Research Program at Winship Cancer Institute. Dr. Dahlman received his PhD from MIT and Harvard Medical School in 2014, where he studied RNA delivery with Robert Langer and Daniel Anderson. He studied RNA design and gene editing as a post-doc with Feng Zhang at the Broad Institute.
Dr. Dahlman is interested in drug delivery, targeted in vivo gene editing, and using genomics to improve biomaterial design. He has designed and synthesized nanoparticles that efficiently deliver RNAs to the lung and heart. These nanoparticles can deliver multiple RNAs at once, and can simultaneously knockdown five genes concurrently in vivo. They have been used by over ten labs across the United States to study cancer, atherosclerosis, inflammation, emphysema, and pulmonary hypertension, and are being evaluated for clinical trials.
RNA-based drugs can turn on (or off) any gene in the genome. However, whether the drug is made out of siRNA, mRNA, lncRNA, or CRISPR, all RNA therapies are limited by one problem: drug delivery. Chemists can design thousands of distinct nanoparticles to deliver RNA. However, after nanoparticles are synthesized, they are tested in in vitro systems which do not have a liver, kidney, spleen, immune system, pulsatile blood flow, or other factors that affect nanoparticle delivery in vivo. To test thousands of nanoparticles in vivo, we designed a series of increasingly advanced DNA barcoding platforms. Our goal is to quantify how up to 500 nanoparticles functionally deliver mRNA or siRNA into up to 40 cell types, all in a single mouse. Since 2016, we have (i) generated nearly 200,000 in vivo drug delivery datapoints, (ii) developed a customized bioinformatics pipeline to iteratively ‘evolve’ nanoparticles that target new cell types in the spleen, liver, and bone marrow, (iii) identified nanoparticles that facilitate Cas9 gene editing outside the liver, (iv) characterized how internal metabolic signaling alters nanoparticle delivery in vivo, and (v) used in vivo synthetic biology to control therapeutic Cas9 editing in new tissues. Our data demonstrate that barcoded LNPs can elucidate fundamental questions about in vivo nanoparticle delivery, and identify nanoparticles for in vivo gene therapies.
Bio:
James Dahlman, PhD, is Assistant Professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech University. He is a member of the Discovery and Developmental Therapeutics Research Program at Winship Cancer Institute. Dr. Dahlman received his PhD from MIT and Harvard Medical School in 2014, where he studied RNA delivery with Robert Langer and Daniel Anderson. He studied RNA design and gene editing as a post-doc with Feng Zhang at the Broad Institute.
Dr. Dahlman is interested in drug delivery, targeted in vivo gene editing, and using genomics to improve biomaterial design. He has designed and synthesized nanoparticles that efficiently deliver RNAs to the lung and heart. These nanoparticles can deliver multiple RNAs at once, and can simultaneously knockdown five genes concurrently in vivo. They have been used by over ten labs across the United States to study cancer, atherosclerosis, inflammation, emphysema, and pulmonary hypertension, and are being evaluated for clinical trials.
Practical information
- Expert
- Free
Organizer
- EPFL / STI / IMX /SuNMIL, Prof. Francesco Stellacci