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SUMMARY:Improving RNA and gene editing therapies by testing thousands of n
 anoparticles in vivo using DNA barcodes
DTSTART:20190415T090000
DTEND:20190415T100000
DTSTAMP:20260916T062913Z
UID:ca32475db3b3104caa5c413d53769b44dc8ff370a6a393f3c87371c2
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof. James E. Dahlman\, PhD\, Dept. of Biomedical Engineerin
 g\, Georgia Institute of Technology\, Emory School of Medicine\, Atlanta\,
  GA (USA)\nAbstract:\nRNA-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. Ho
 wever\, after nanoparticles are synthesized\, they are tested in in vitro
  systems which do not have a liver\, kidney\, spleen\, immune system\, pu
 lsatile blood flow\, or other factors that affect nanoparticle delivery i
 n 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 cus
 tomized 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 li
 ver\, (iv) characterized how internal metabolic signaling alters nanoparti
 cle delivery in vivo\, and (v) used in vivo synthetic biology to contr
 ol therapeutic Cas9 editing in new tissues. Our data demonstrate that bar
 coded LNPs can elucidate fundamental questions about in vivo nanoparticl
 e delivery\, and identify nanoparticles for in vivo gene therapies.\n\nB
 io:\nJames Dahlman\, PhD\, is Assistant Professor in the Wallace H. Coulte
 r Department of Biomedical Engineering at Georgia Tech University. He is
  a member of the Discovery and Developmental Therapeutics Research Progr
 am at Winship Cancer Institute. Dr. Dahlman received his PhD from MIT and 
 Harvard Medical School in 2014\, where he studied RNA delivery with Rober
 t Langer and Daniel Anderson. He studied RNA design and gene editing as 
 a post-doc with Feng Zhang at the Broad Institute. \nDr. Dahlman is inte
 rested in drug delivery\, targeted in vivo gene editing\, and using genom
 ics to improve biomaterial design. He has designed and synthesized nanopa
 rticles that efficiently deliver RNAs to the lung and heart. These nanop
 articles can deliver multiple RNAs at once\, and can simultaneously knock
 down five genes concurrently in vivo. They have been used by over ten lab
 s across the United States to study cancer\, atherosclerosis\, inflammat
 ion\, emphysema\, and pulmonary hypertension\, and are being evaluated fo
 r clinical trials.
LOCATION:BC 03 https://plan.epfl.ch/?room==BC%2003
STATUS:CONFIRMED
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