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Syngeneic AAV Pseudo-particles Potentiate Gene Transduction of AAV Vectors.

Abstract：

:Adeno-associated virus (AAV) vectors have emerged as a safe and efficient gene therapy platform. One complication is that a significant amount of empty particles have always been generated as impurities during AAV vector production. However, the effects of such particles on AAV vector performance remain unclear. Here we systemically evaluated the biological properties of three types of "empty" AAV particles: syngeneic pseudo-vectors with partial AAV genomes derived from DNA of the corresponding full particles, allogeneic pseudo-vectors with partial genomes different from the corresponding full particles, and null pseudo-vectors with no DNA inside the capsids. The syngeneic particles in excess increased the corresponding full AAV vector transgene expression both in vivo and in vitro. However, such effects were not observed with null or allogeneic particles. The observed differences among these pseudo-AAV particles may be ascribed to the syngeneic pseudo-vector DNA facilitating the complementary DNA synthesis of the corresponding full AAV particles. Our study suggests that the DNA content in the pseudo-vectors plays a key role in dictating their effects on AAV transduction. The effects of residual "empty" particles should be adequately assessed when comparing AAV vector performance. The syngeneic AAV pseudo-vectors may be used to enhance the efficacy of gene therapy.

journal_name

Mol Ther Methods Clin Dev

journal_title

Molecular therapy. Methods & clinical development

authors

Wang Q,Dong B,Pokiniewski KA,Firrman J,Wu Z,Chin MP,Chen X,Liu L,Xu R,Diao Y,Xiao W

doi

10.1016/j.omtm.2016.12.004

subject

Has Abstract

pub_date

2016-12-24 00:00:00

pages

149-158

issn

2329-0501

pii

S2329-0501(16)30137-1

journal_volume

4

pub_type

杂志文章

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