| RRC ID |
89864
|
| Author |
Mensah EO, Nishimura K, Morishita K, Kato Y, Fukuda A, Sumaru K, Hisatake K, Sano M.
|
| Title |
Enhancing the utility of Sendai virus-based vectors through antiviral compound-mediated removal.
|
| Journal |
J Biotechnol
|
| Abstract |
Sendai virus (SeV)-based vectors are recognized as potential tools in gene therapy and regenerative medicine as they can express transgenes without chromosomal insertion. We previously reported that a replication-defective and persistent SeV (SeVdp) vector capable of long-term and multiple transgene expression can promote reprogramming of somatic cells into induced pluripotent stem (iPS) cells. Importantly, siRNA- and miRNA-mediated suppression of the SeV RNA-dependent RNA polymerase facilitates removal of SeVdp vectors from reprogrammed cells, resulting in establishing transgene-free iPS cells. However, these approaches are considerably dependent on transfection efficiency and intracellular miRNA activity, respectively. In this study, we assessed a simple approach to eliminate SeVdp vectors from infected cells using antiviral agents. GHP-88309, an antiviral compound against a broad range of paramyxoviruses, effectively inhibited SeV replication and enabled the removal of SeVdp vectors. Notably, this compound allowed complete elimination of a BRN4-expressing SeVdp vector from neural stem cells after enforced differentiation of embryonic stem cells. Our findings suggest that GHP-88309 would be an effective agent to enhance the utility and flexibility of SeVdp vectors in various biological and medical applications including transcription factor-mediated cell differentiation.
|
| Volume |
414
|
| Pages |
176-185
|
| Published |
2026-6-1
|
| DOI |
10.1016/j.jbiotec.2026.03.018
|
| PII |
S0168-1656(26)00090-8
|
| PMID |
41856291
|
| MeSH |
Animals
Antiviral Agents* / pharmacology
Cell Differentiation / drug effects
Genetic Vectors* / genetics
Humans
Neural Stem Cells / cytology
Sendai virus* / drug effects
Sendai virus* / genetics
Virus Replication / drug effects
|
| Resource |
| Human and Animal Cells |
HCT116(RCB2979) |
