Environment acidity triggers release of recombinant adeno-associated virus serotype 2 from a tunable matrix

J Control Release. 2013 Sep 10;170(2):252-8. doi: 10.1016/j.jconrel.2013.05.009. Epub 2013 May 20.

Abstract

Successful design of a pH responsive polyelectrolyte-based virus delivery matrix with extracellular release triggered by tumor acidosis has been achieved. Recombinant adeno-associated virus serotype 2 (AAV2) is loaded in the polyelectrolyte-based matrix (AAV2-matrix), which is formed by a biodegradable copolymer of poly(polyethylene glycol-1-(3-aminopropyl)imidazole-dl-aspartic acid) with tuned pH response based on inclusion of polyethyleneimine (PEI(800)). Physico-chemical properties of AAV2-matrix are optimized to minimize cellular interactions until a tumor acidosis-like environment protonates the matrix, reverses ζ-potential and causes particles to swell, releasing the AAV2 virus. The pH-dependent release is highly controllable and potentially useful to optimize site specific viral delivery.

Keywords: Gene delivery; Localized delivery; Recombinant adeno-associated virus; Transduction; pH-sensitive vector.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival
  • Dependovirus*
  • Green Fluorescent Proteins / genetics*
  • HeLa Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Mice
  • Mice, Nude
  • NIH 3T3 Cells
  • Neoplasms / metabolism*
  • Polymers / chemistry
  • Transduction, Genetic*

Substances

  • Polymers
  • Green Fluorescent Proteins