Abstract
HIV-1 gene therapy offers a promising alternative to small molecule antiretroviral treatments and current vaccination strategies by transferring, into HIV-1-susceptible cells, the genetic ability to resist infection. The need for novel and innovative strategies to prevent and treat HIV-1 infection is critical due to devastating effects of the virus in developing countries, high cost, toxicity, generation of escape mutants from antiretroviral therapies, and the failure of past and current vaccination efforts. As a first step toward achieving this goal, an HIV-1-susceptible cell-specific targeting vector was evaluated to selectively transfer, into CCR5-positive target cells, an anti-HIV CCR5 shRNA gene for subsequent knockdown of CCR5 expression and protection from HIV-1 infection. Using a ZZ domain/monoclonal antibody-conjugated Sindbis virus glycoprotein pseudotyped lentiviral vector, here we demonstrate the utility of this strategy for HIV-1 gene therapy by specifically targeting HIV-1-susceptible cells and engineering these cells to resist HIV-1 infection. CCR5-positive human cells were successfully and specifically targeted in vitro and in vivo for transduction by a lentiviral vector expressing a highly potent CCR5 shRNA which conferred resistance to HIV-1 infection. Here we report the initial evaluation of this targeting vector for HIV-1 gene therapy in a preexposure prophylactic setting.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 152-161 |
| Number of pages | 10 |
| Journal | Journal of Acquired Immune Deficiency Syndromes |
| Volume | 52 |
| Issue number | 2 |
| DOIs | |
| State | Published - Oct 2009 |
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Keywords
- CCR5 shRNA
- HIV gene therapy
- HIV preexposure prophylaxis
- Lentiviral vector
- Targeting vector
ASJC Scopus subject areas
- Infectious Diseases
- Pharmacology (medical)
Cite this
Specific transduction of hiv-susceptible cells for CCR5 knockdown and resistance to HIV infection : A novel method for targeted gene therapy and intracellular immunization. / Anderson, Joseph S; Walker, Jon; Nolta, Jan; Bauer, Gerhard.
In: Journal of Acquired Immune Deficiency Syndromes, Vol. 52, No. 2, 10.2009, p. 152-161.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Specific transduction of hiv-susceptible cells for CCR5 knockdown and resistance to HIV infection
T2 - A novel method for targeted gene therapy and intracellular immunization
AU - Anderson, Joseph S
AU - Walker, Jon
AU - Nolta, Jan
AU - Bauer, Gerhard
PY - 2009/10
Y1 - 2009/10
N2 - HIV-1 gene therapy offers a promising alternative to small molecule antiretroviral treatments and current vaccination strategies by transferring, into HIV-1-susceptible cells, the genetic ability to resist infection. The need for novel and innovative strategies to prevent and treat HIV-1 infection is critical due to devastating effects of the virus in developing countries, high cost, toxicity, generation of escape mutants from antiretroviral therapies, and the failure of past and current vaccination efforts. As a first step toward achieving this goal, an HIV-1-susceptible cell-specific targeting vector was evaluated to selectively transfer, into CCR5-positive target cells, an anti-HIV CCR5 shRNA gene for subsequent knockdown of CCR5 expression and protection from HIV-1 infection. Using a ZZ domain/monoclonal antibody-conjugated Sindbis virus glycoprotein pseudotyped lentiviral vector, here we demonstrate the utility of this strategy for HIV-1 gene therapy by specifically targeting HIV-1-susceptible cells and engineering these cells to resist HIV-1 infection. CCR5-positive human cells were successfully and specifically targeted in vitro and in vivo for transduction by a lentiviral vector expressing a highly potent CCR5 shRNA which conferred resistance to HIV-1 infection. Here we report the initial evaluation of this targeting vector for HIV-1 gene therapy in a preexposure prophylactic setting.
AB - HIV-1 gene therapy offers a promising alternative to small molecule antiretroviral treatments and current vaccination strategies by transferring, into HIV-1-susceptible cells, the genetic ability to resist infection. The need for novel and innovative strategies to prevent and treat HIV-1 infection is critical due to devastating effects of the virus in developing countries, high cost, toxicity, generation of escape mutants from antiretroviral therapies, and the failure of past and current vaccination efforts. As a first step toward achieving this goal, an HIV-1-susceptible cell-specific targeting vector was evaluated to selectively transfer, into CCR5-positive target cells, an anti-HIV CCR5 shRNA gene for subsequent knockdown of CCR5 expression and protection from HIV-1 infection. Using a ZZ domain/monoclonal antibody-conjugated Sindbis virus glycoprotein pseudotyped lentiviral vector, here we demonstrate the utility of this strategy for HIV-1 gene therapy by specifically targeting HIV-1-susceptible cells and engineering these cells to resist HIV-1 infection. CCR5-positive human cells were successfully and specifically targeted in vitro and in vivo for transduction by a lentiviral vector expressing a highly potent CCR5 shRNA which conferred resistance to HIV-1 infection. Here we report the initial evaluation of this targeting vector for HIV-1 gene therapy in a preexposure prophylactic setting.
KW - CCR5 shRNA
KW - HIV gene therapy
KW - HIV preexposure prophylaxis
KW - Lentiviral vector
KW - Targeting vector
UR - http://www.scopus.com/inward/record.url?scp=70349683000&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349683000&partnerID=8YFLogxK
U2 - 10.1097/QAI.0b013e3181b010a0
DO - 10.1097/QAI.0b013e3181b010a0
M3 - Article
C2 - 19593160
AN - SCOPUS:70349683000
VL - 52
SP - 152
EP - 161
JO - Journal of acquired immune deficiency syndromes (1999)
JF - Journal of acquired immune deficiency syndromes (1999)
SN - 1525-4135
IS - 2
ER -