| RRC ID |
54331
|
| 著者 |
Suzuki N, Yoshida T, Takeuchi H, Sakuma R, Sukegawa S, Yamaoka S.
|
| タイトル |
Robust Enhancement of Lentivirus Production by Promoter Activation.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Lentiviral vectors are a valuable tool to deliver exogenous genes for stable expression in cells. While much progress has been made in processing lentiviral vector-containing culture medium, it remains to be explored how the production of lentiviral vector from producer cells can be increased. We initially found that co-expression of the SPRY domain-containing SOCS box protein 1 (SPSB1) promotes the production of human immunodeficiency virus type 1 (HIV-1) and lentiviral vector with increased expression of the Gag and envelope proteins and activation of the HIV-1 LTR and CMV promoter. The presence of AP-1, NF-κB and CREB/ATF recognition sites in these promoters prompted us to utilize human T-lymphotropic virus type 1 (HTLV-1) Tax for lentiviral vector production because Tax activates all these transcription factors. Co-expression of a small amount of Tax markedly increased both the expression of viral structural proteins in producer cells and release of lentiviral vector particles, resulting in a more than 10-fold enhancement of transduction efficiency. Of note, the Tax protein was not detected in the lentiviral vector particles concentrated by ultracentrifugation, supporting the safety of this preparation. Collectively, these results indicate that promoter activation in producer cells represents a promising approach to preparing high-titer lentiviral vectors.
|
| 巻・号 |
8(1)
|
| ページ |
15036
|
| 公開日 |
2018-10-11
|
| DOI |
10.1038/s41598-018-33042-5
|
| PII |
10.1038/s41598-018-33042-5
|
| PMID |
30310119
|
| PMC |
PMC6181906
|
| MeSH |
Cell Line
Gene Products, tax / metabolism
Gene Transfer Techniques
Genetic Engineering*
Genetic Vectors / genetics*
HIV-1 / genetics
Host-Pathogen Interactions
Human T-lymphotropic virus 1 / genetics
Humans
Lentivirus / physiology*
Lentivirus Infections / metabolism
Lentivirus Infections / virology
Promoter Regions, Genetic*
Protein Binding
Suppressor of Cytokine Signaling Proteins / metabolism
Terminal Repeat Sequences
Transduction, Genetic
Transfection
Virus Replication*
|
| IF |
3.998
|
| 引用数 |
1
|
| リソース情報 |
| 遺伝子材料 |
CSII-CMV-MCS-IRES2-Bsd (RDB04385) |
