Synopsis: Genetic drugs are limited by inefficient delivery to target cells, and unwanted delivery to off-target cells. Thousands of chemically distinct lipid nanoparticles (LNPs) can be synthesized to deliver genetic drugs. These nanoparticle libraries are then studied in vitro, before a small number of nanoparticles is selected for in vivo analysis. Here we have used high throughput LNP DNA barcoding to study how well hundreds of nanoparticles delivered genetic drugs in vivo. We used these data to study 2 fundamental questions in drug delivery. First, how does LNP delivery change within the microenvironment of a target tissue? Second, how do genetic and physiological perturbations influence delivery to cell types in vivo? Our data demonstrate that barcoded LNPs can be used to efficiently study fundamental questions in nanoparticle science directly in vivo, and quickly identify promising candidates for further pre-clinical evaluation.

Short Bio: James Dahlman is an Assistant Professor in the Georgia Tech BME Department. He studied gene editing with Feng Zhang and RNA delivery with Robert Langer and Daniel Anderson. The Lab for Precision Therapies at Georgia Tech works at the interface of drug delivery, nanotechnology, genomics, and gene editing. James has designed nanoparticles that deliver RNA to blood vessels in the heart and lung and work robustly in non-human primates. He has developed targeted combination therapies targeting 5 genes at once in vivo.

James also uses molecular biology to design the genetic drugs he delivers. He designed ‘dead’ guide RNAs; these guides can turn on genes using catalytically active Cas9. Similarly, using his background in nanoparticle chemistry, in vivo RNA delivery, and genomics, his lab designed a nanoparticle DNA barcoding system to measure how >200 nanoparticles target cells in a single mouse, directly in vivo.

James Dahlman has won the NSF, NDSEG, NIH OxCam, Whitaker, and LSRF Fellowships, the Weintraub Graduate Thesis Award, and was recently named a Bayer Young Investigator and Parkinson’s Disease Foundation Young Investigator. His work has been published in Nature Nano, Nature Biotech, Nature Cell Bio, Science Trans Med, Cell, PNAS, and other leading journals. 

Keywords

Drug delivery, genetic drugs, RNA therapies, nanotechnology, lipid nanoparticles (LNPs), cardiovascular / pulmonary Engineering

Additional Information:

www.dahlmanlab.org

https://www.bme.gatech.edu/bme/next-frontier-medicine