SEARCH FOR THE HYDROGEN ATOM OF VIRUSES: VIRUS-LIKE-PARTICLE DELIVERY OF SELF-REPLICATING GENES

by Prof. William Gelbart

Dept. Of Chemistry And Biochemistry, University Of California At Los Angeles

at Biological and soft-matter physics

Thu, 10 Jun 2021, 9:10
ZOOM only - Meeting ID: 874 2021 0979 - PLEASE NOTE CHANGE OF TIME

Abstract

Positive-sense-RNA viruses are among the simplest of all viruses, because their life cycle takes place entirely in the cytoplasm of host cells, with no need to control the traffic of viral components into and out of the nucleus. Related to this fact, their genome is a messenger RNA (mRNA) molecule that is translated directly by ribosomes. The first viral protein synthesized is an RNA-dependent RNA polymerase – an RNA replicase – that strongly replicates the genome, making up to a million copies within hours. Further, in the case of a two-gene virus – the “hydrogen atom” of viruses – the second gene product is a capsid protein that spontaneously packages and protects the RNA genes. These viruses are also among the few that can be “made from scratch”, i.e., reconstituted in vitro by simply mixing their purified components – RNA and capsid protein.
Exploiting these facts, we use the capsid protein of a particular plant virus and the RNA replicase gene of a particular insect virus to in vitro reconstitute hybrid virus-like particles (VLPs) that contain an RNA replicase gene to which has been added genetic information of interest, such as a therapeutic gene or an mRNA vaccine. The capsid protein is unique in that it packages each of a broad range of heterologous (non-viral) RNA molecules, and the RNA replicase is unique in that it works in a broad range of mammalian cells.
In my talk I discuss the physics underlying the self-assembly of these VLPs and describe several applications involving the delivery of VLP-protected/targeted self-amplifying RNA viral vaccines and cancer therapeutics.

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https://us02web.zoom.us/j/87420210979

Meeting ID: 874 2021 0979

Created on 25-04-2021 by Granek, Rony (rgranek)
Updaded on 09-06-2021 by Granek, Rony (rgranek)