Adeno-associated virus vector-mediated transgene integration into neurons and other nondividing cell targets

Ping Wu, M. Ian Phillips, John Bui, Ernest F. Terwilliger

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

The site-specific integration of wild-type adeno-associated virus (wtAAV) into the human genome is a very attractive feature for the development of AAV-based gene therapy vectors. However, knowledge about integration of wtAAV, as well as currently configured recombinant AAV (rAAV) vectors, is limited. By using a modified Alu-PCR technique to amplify and sequence the vector-cellular junctions, we provide the first direct evidence both in vitro and in vivo of rAAV-mediated transgene integration in several types of nondividing cells, including neurons. This novel technique will be highly useful for further delineating the mechanisms underlying AAV-mediated integration, including issues of frequency, site preference, and DNA rearrangement in human as well as animal cells. Results from these studies should be beneficial for the development of the next generation of gene delivery vectors.

Original languageEnglish (US)
Pages (from-to)5919-5926
Number of pages8
JournalJournal of Virology
Volume72
Issue number7
StatePublished - Jul 1998
Externally publishedYes

Fingerprint

Dependovirus
Transgenes
transgenes
neurons
Neurons
gene therapy
Gene Rearrangement
Human Genome
gene transfer
Genetic Therapy
cells
Polymerase Chain Reaction
genome
DNA
methodology
Genes
animals

ASJC Scopus subject areas

  • Immunology

Cite this

Adeno-associated virus vector-mediated transgene integration into neurons and other nondividing cell targets. / Wu, Ping; Phillips, M. Ian; Bui, John; Terwilliger, Ernest F.

In: Journal of Virology, Vol. 72, No. 7, 07.1998, p. 5919-5926.

Research output: Contribution to journalArticle

Wu, Ping ; Phillips, M. Ian ; Bui, John ; Terwilliger, Ernest F. / Adeno-associated virus vector-mediated transgene integration into neurons and other nondividing cell targets. In: Journal of Virology. 1998 ; Vol. 72, No. 7. pp. 5919-5926.
@article{41dc13bf3fc74f59951a924926efea45,
title = "Adeno-associated virus vector-mediated transgene integration into neurons and other nondividing cell targets",
abstract = "The site-specific integration of wild-type adeno-associated virus (wtAAV) into the human genome is a very attractive feature for the development of AAV-based gene therapy vectors. However, knowledge about integration of wtAAV, as well as currently configured recombinant AAV (rAAV) vectors, is limited. By using a modified Alu-PCR technique to amplify and sequence the vector-cellular junctions, we provide the first direct evidence both in vitro and in vivo of rAAV-mediated transgene integration in several types of nondividing cells, including neurons. This novel technique will be highly useful for further delineating the mechanisms underlying AAV-mediated integration, including issues of frequency, site preference, and DNA rearrangement in human as well as animal cells. Results from these studies should be beneficial for the development of the next generation of gene delivery vectors.",
author = "Ping Wu and Phillips, {M. Ian} and John Bui and Terwilliger, {Ernest F.}",
year = "1998",
month = "7",
language = "English (US)",
volume = "72",
pages = "5919--5926",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "7",

}

TY - JOUR

T1 - Adeno-associated virus vector-mediated transgene integration into neurons and other nondividing cell targets

AU - Wu, Ping

AU - Phillips, M. Ian

AU - Bui, John

AU - Terwilliger, Ernest F.

PY - 1998/7

Y1 - 1998/7

N2 - The site-specific integration of wild-type adeno-associated virus (wtAAV) into the human genome is a very attractive feature for the development of AAV-based gene therapy vectors. However, knowledge about integration of wtAAV, as well as currently configured recombinant AAV (rAAV) vectors, is limited. By using a modified Alu-PCR technique to amplify and sequence the vector-cellular junctions, we provide the first direct evidence both in vitro and in vivo of rAAV-mediated transgene integration in several types of nondividing cells, including neurons. This novel technique will be highly useful for further delineating the mechanisms underlying AAV-mediated integration, including issues of frequency, site preference, and DNA rearrangement in human as well as animal cells. Results from these studies should be beneficial for the development of the next generation of gene delivery vectors.

AB - The site-specific integration of wild-type adeno-associated virus (wtAAV) into the human genome is a very attractive feature for the development of AAV-based gene therapy vectors. However, knowledge about integration of wtAAV, as well as currently configured recombinant AAV (rAAV) vectors, is limited. By using a modified Alu-PCR technique to amplify and sequence the vector-cellular junctions, we provide the first direct evidence both in vitro and in vivo of rAAV-mediated transgene integration in several types of nondividing cells, including neurons. This novel technique will be highly useful for further delineating the mechanisms underlying AAV-mediated integration, including issues of frequency, site preference, and DNA rearrangement in human as well as animal cells. Results from these studies should be beneficial for the development of the next generation of gene delivery vectors.

UR - http://www.scopus.com/inward/record.url?scp=0031779697&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031779697&partnerID=8YFLogxK

M3 - Article

C2 - 9621054

AN - SCOPUS:0031779697

VL - 72

SP - 5919

EP - 5926

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 7

ER -