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Targeting of lentiviral vectors mediated by RNA aptamers

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)

FDA/CBER

MOLBIO-21

Authors

  • M Panigaj
  • M Marino
  • J Reiser

Abstract

Viral vectors provide powerful tools for transgene delivery. The ability to selectively target gene delivery vectors to target cells in vitro and in vivo remains a challenge. Recently, RNA aptamers have been shown to have the capacity to deliver therapeutic agents such as siRNAs, chemotherapeutic drugs, and nanoparticles in a cell-specific manner. To investigate whether the tropism of lentiviral vectors can be altered using specific RNA aptamers, we created lentiviral vector pseudotypes bearing measles virus derived glycoproteins including the F protein and a receptor-blind variant of the H protein displaying a bacteriophage lambda N protein-derived RNA binding domain. An RNA scaffold was designed to simultaneously bind the vector particle and an RNA aptamer specific for the human epidermal growth factor receptor (EGFR), thereby conferring to the vector particle its cell targeting specificity. The results obtained show that binding of vector particles to target cells is mediated by RNA since treatment with RNases reduced the transduction efficiency. Furthermore, RNA aptamer-mediated binding of the vector to cells was prevented using soluble, recombinant EGFR. Our ongoing research is focused on optimizing the conditions for aptamer-mediated lentiviral vector transduction.

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