title: 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.
authors.affiliation: School of Biomedical Sciences, Huaqiao University, Quanzhou, Fujian 362021, China; Sol Sherry Thrombosis Research Center, Temple University, Philadelphia, PA 19122, USA.
authors.forename: Qizhao
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Sol Sherry Thrombosis Research Center, Temple University, Philadelphia, PA 19122, USA.
authors.forename: Biao
authors.initials: B
authors.lastname: Dong
authors.affiliation: Department of Microbiology and Immunology, Temple University, Philadelphia, PA 19122, USA.
authors.forename: Katie A
authors.initials: KA
authors.lastname: Pokiniewski
authors.affiliation: Department of Microbiology and Immunology, Temple University, Philadelphia, PA 19122, USA; United States Department of Agriculture, ARS, ERRC, Wyndmoor, PA 19038, USA.
authors.forename: Jenni
authors.initials: J
authors.lastname: Firrman
authors.affiliation: Sol Sherry Thrombosis Research Center, Temple University, Philadelphia, PA 19122, USA.
authors.forename: Zhongren
authors.initials: Z
authors.lastname: Wu
authors.affiliation: School of Biomedical Sciences, Huaqiao University, Quanzhou, Fujian 362021, China.
authors.forename: Mario P S
authors.initials: MP
authors.lastname: Chin
authors.affiliation: Cardiovascular Research Center, Temple University, Philadelphia, PA 19122, USA.
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Chen
authors.affiliation: United States Department of Agriculture, ARS, ERRC, Wyndmoor, PA 19038, USA.
authors.forename: LinShu
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Biomedical Sciences, Huaqiao University, Quanzhou, Fujian 362021, China.
authors.forename: Ruian
authors.initials: R
authors.lastname: Xu
authors.affiliation: School of Biomedical Sciences, Huaqiao University, Quanzhou, Fujian 362021, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Diao
authors.affiliation: School of Biomedical Sciences, Huaqiao University, Quanzhou, Fujian 362021, China; Sol Sherry Thrombosis Research Center, Temple University, Philadelphia, PA 19122, USA; Department of Microbiology and Immunology, Temple University, Philadelphia, PA 19122, USA; Cardiovascular Research Center, Temple University, Philadelphia, PA 19122, USA; United States Department of Agriculture, ARS, ERRC, Wyndmoor, PA 19038, USA.
authors.forename: Weidong
authors.initials: W
authors.lastname: Xiao
keywords: DI particles; adeno-associated virus; gene therapy