Development of an RNA virus-based episomal vector with artificial aptazyme for gene silencing.
Aptazyme
Borna virus vector
Gene regulation
Viral vector
Journal
Applied microbiology and biotechnology
ISSN: 1432-0614
Titre abrégé: Appl Microbiol Biotechnol
Pays: Germany
ID NLM: 8406612
Informations de publication
Date de publication:
18 Oct 2024
18 Oct 2024
Historique:
received:
15
05
2024
accepted:
07
10
2024
revised:
04
09
2024
medline:
18
10
2024
pubmed:
18
10
2024
entrez:
18
10
2024
Statut:
epublish
Résumé
RNA virus-based episomal vector (REVec), engineered from Borna disease virus, is an innovative gene delivery tool that enables sustained gene expression in transduced cells. However, the difficulty in controlling gene expression and eliminating vectors has limited the practical use of REVec. In this study, we overcome these shortcomings by inserting artificial aptazymes into the untranslated regions of foreign genes carried in vectors or downstream of the viral phosphoprotein gene, which is essential for vector replication. Non-transmissive REVec carrying GuaM8HDV or the P1-F5 aptazyme showed immediate suppression of gene expression in a guanine or theophylline concentration-dependent manner. Continuous compound administration also markedly reduced the percentage of vector-transduced cells and eventually led to the complete elimination of the vectors from the transduced cells. This new REVec is a safe gene delivery technology that allows fine-tuning of gene expression and could be a useful platform for gene therapy and gene-cell therapy, potentially contributing to the cure of many genetic disorders. KEY POINTS: • We developed a bornavirus vector capable of silencing transgene expression by insertion of aptazyme • Transgene expression was markedly suppressed in a compound concentration-dependent manner • Artificial aptazyme systems allowed complete elimination of the vector from transduced cells.
Identifiants
pubmed: 39422780
doi: 10.1007/s00253-024-13327-8
pii: 10.1007/s00253-024-13327-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
491Subventions
Organisme : Japan Society for the Promotion of Science
ID : JP19K22530
Organisme : Japan Society for the Promotion of Science
ID : JP20H05682
Organisme : Japan Society for the Promotion of Science
ID : JP21K19909
Organisme : Japan Society for the Promotion of Science
ID : 22K20759
Organisme : Program for Creating STart-ups from Advanced Research and Technology
ID : JPMJST2113
Organisme : Japan Agency for Medical Research and Development
ID : JP23bm1223017
Informations de copyright
© 2024. The Author(s).
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