Charge switching lipid nanoparticles deliver nucleic acids without triggering inflammation

Host

Miguel Seabra, PhD, Ocular Low-cost Gene Therapy

Venue

Seminar Room

Abstract

Lipid nanoparticles (LNPs) have great potential for delivering nucleic acids, however they trigger the production of inflammatory cytokines and this limits their medical applications. Developing LNPs that do not trigger the production of cytokines is challenging because the LNP’s ionizable lipid and the process of endosomal disruption are the major sources of LNP toxicity, and are also essential for delivering nucleic acids. In this presentation, I will present a new class of LNPs that switch their charged states between the pHs of 7.4 and 4.0, and can deliver nucleic acids efficiently without triggering inflammation, termed the switchable nanoparticles (SNPs). The SNPs deliver mRNA and pDNA as efficiently as traditional LNPs in vitro and in vivo, but do not activate the TLR4, complement, galectin-8 and platelet activating factor (PAF) signaling pathways, and consequently have lower toxicity than traditional LNPs. In addition, SNPs are better at treating LPS-induced acute lung injury than traditional LNPs because they do not exacerbate pre-existing inflammation. We anticipate numerous applications of the SNPs because of their ability to deliver nucleic acids efficiently without triggering inflammation.

Bio

Dr. Niren Murthy is a professor in the Department of Bioengineering at the University of California at Berkeley and a member of the Innovative Genomics Institute. Dr. Murthy was an assistant professor at Georgia Tech’s BME department from 2003-2012. Dr. Murthy’s scientific career has focused on the molecular design and synthesis of new materials for drug delivery and molecular imaging. The Murthy laboratory is currently focused on developing next generation lipid nanoparticles that can deliver mRNA and gene editing enzymes in vivo. Several start-up companies and licenses have been generated from the laboratory, in particular, the start-up companies GenEdit (now BreezeBio), BioAmp Diagnostics, Microbial Medical and Opus Biosciences were formed based upon research conducted in the Murthy lab.

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About CR Colloquia Series

Champalimaud Research (CR) Colloquia Series is a seminar programme organised by the Champalimaud Centre for the Unknown to promote the discussion about the most interesting and significant questions in neuroscience and physiology & cancer with appointed speakers by the CR Community.