Recorded on: May 27, 2021 2:00 pm CT
Presenter: Dr. James Dahlman, Assistant Professor, Georgia Institute of Technology & Emory University School of Medicine, USA.
This webinar was based upon the paper 'Nanoparticles containing constrained phospholipids deliver mRNA to liver immune cells in vivo without targeting ligands', winner of the 2021 AOCS Phospholipid Division Best Paper Award.
Read the award winning article.
DNA and RNA can manipulate the expression of any gene, making these molecules promising drugs. However, whether the drug is comprised of DNA, siRNA, mRNA, lncRNA, or another nucleic acid, it is limited by one problem: drug delivery. Chemists design thousands of distinct nanoparticles to deliver DNA or RNA to the desired cell type. However, after nanoparticles are synthesized, their ability to deliver drugs is evaluated using in vitro systems devoid of a liver, kidney, spleen, immune system, pulsatile blood flow, and other selection pressures known to affect nanoparticle delivery in vivo.
We had designed a series of increasingly advanced DNA barcoding platforms to quantify how thousands of nanoparticles deliver nucleic acids in vivo. Our goal was to quantify how up to 300 nanoparticles deliver DNA, mRNA, ASOs, or siRNA into up to 30 cell types, all in a single animal. To analyze these large in vivo drug delivery datasets, we had also developed an open source bioinformatics pipeline to iteratively ‘evolve’ nanoparticles that target cells in vivo. Using this high throughput, iterative, in vivo approach, we had identified nanoparticles with tropism to many novel cell types, in many different tissues.