Abstract
Lentiviral vectors derived from the human immunodeficiency virus-1 (HIV-1) have a higher propensity to transduce nondividing cells compared to vectors based on oncoretroviruses. We report here that genistein, a previously known protein tyrosine kinase (PTK) inhibitor and G2 cell cycle arrest inducer, significantly enhanced lentiviral transduction in a dose-dependent manner. Increased transduction, as measured by vector expression, was seen in a variety of human cell lines, murine primary lymphocytes, and primary human CD34+ peripheral blood progenitor cells as well. Increased vector expression was also associated with an increase in vector DNA copy number, as assessed by quantitative PCR. Genistein-mediated G2 cell cycle arrest, rather than PTK inhibition, appears to be the major factor responsible for increased gene transfer. Genistein also increases cyclophilin A (CypA) protein, a cellular protein important for efficient HIV-1 infection. While we show that CypA-/- Jurkat cells transduce poorly with lentiviral vectors, genistein does increase gene transfer in CypA-deficient cells. CypA and G2 cell cycle arrest appear to be two independent factors important for efficient lentiviral gene transfer. The role of genistein and other G2-arresting agents may be useful for improving the efficiency of lentiviral gene therapy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 546-554 |
| Number of pages | 9 |
| Journal | Molecular Therapy |
| Volume | 14 |
| Issue number | 4 |
| DOIs | |
| State | Published - Oct 1 2006 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology
- Genetics
- Pharmacology
- Drug Discovery
Cite this
}
G2 Cell Cycle Arrest and Cyclophilin A in Lentiviral Gene Transfer. / Zhang, Shangming; Joseph, Guiandre; Pollok, Karen; Berthoux, Lionel; Sastry, Lakshmi; Luban, Jeremy; Cornetta, Kenneth.
In: Molecular Therapy, Vol. 14, No. 4, 01.10.2006, p. 546-554.Research output: Contribution to journal › Article
TY - JOUR
T1 - G2 Cell Cycle Arrest and Cyclophilin A in Lentiviral Gene Transfer
AU - Zhang, Shangming
AU - Joseph, Guiandre
AU - Pollok, Karen
AU - Berthoux, Lionel
AU - Sastry, Lakshmi
AU - Luban, Jeremy
AU - Cornetta, Kenneth
PY - 2006/10/1
Y1 - 2006/10/1
N2 - Lentiviral vectors derived from the human immunodeficiency virus-1 (HIV-1) have a higher propensity to transduce nondividing cells compared to vectors based on oncoretroviruses. We report here that genistein, a previously known protein tyrosine kinase (PTK) inhibitor and G2 cell cycle arrest inducer, significantly enhanced lentiviral transduction in a dose-dependent manner. Increased transduction, as measured by vector expression, was seen in a variety of human cell lines, murine primary lymphocytes, and primary human CD34+ peripheral blood progenitor cells as well. Increased vector expression was also associated with an increase in vector DNA copy number, as assessed by quantitative PCR. Genistein-mediated G2 cell cycle arrest, rather than PTK inhibition, appears to be the major factor responsible for increased gene transfer. Genistein also increases cyclophilin A (CypA) protein, a cellular protein important for efficient HIV-1 infection. While we show that CypA-/- Jurkat cells transduce poorly with lentiviral vectors, genistein does increase gene transfer in CypA-deficient cells. CypA and G2 cell cycle arrest appear to be two independent factors important for efficient lentiviral gene transfer. The role of genistein and other G2-arresting agents may be useful for improving the efficiency of lentiviral gene therapy.
AB - Lentiviral vectors derived from the human immunodeficiency virus-1 (HIV-1) have a higher propensity to transduce nondividing cells compared to vectors based on oncoretroviruses. We report here that genistein, a previously known protein tyrosine kinase (PTK) inhibitor and G2 cell cycle arrest inducer, significantly enhanced lentiviral transduction in a dose-dependent manner. Increased transduction, as measured by vector expression, was seen in a variety of human cell lines, murine primary lymphocytes, and primary human CD34+ peripheral blood progenitor cells as well. Increased vector expression was also associated with an increase in vector DNA copy number, as assessed by quantitative PCR. Genistein-mediated G2 cell cycle arrest, rather than PTK inhibition, appears to be the major factor responsible for increased gene transfer. Genistein also increases cyclophilin A (CypA) protein, a cellular protein important for efficient HIV-1 infection. While we show that CypA-/- Jurkat cells transduce poorly with lentiviral vectors, genistein does increase gene transfer in CypA-deficient cells. CypA and G2 cell cycle arrest appear to be two independent factors important for efficient lentiviral gene transfer. The role of genistein and other G2-arresting agents may be useful for improving the efficiency of lentiviral gene therapy.
UR - http://www.scopus.com/inward/record.url?scp=33748043344&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748043344&partnerID=8YFLogxK
U2 - 10.1016/j.ymthe.2006.05.022
DO - 10.1016/j.ymthe.2006.05.022
M3 - Article
C2 - 16901758
AN - SCOPUS:33748043344
VL - 14
SP - 546
EP - 554
JO - Molecular Therapy
JF - Molecular Therapy
SN - 1525-0016
IS - 4
ER -