Multigene human artificial chromosome vector delivery with herpes simplex virus 1 amplicons
| Autor: | Zoia L. Monaco, David Yl Chan, Daniela Moralli, Julia D Jankowska, Lucy Wheatley |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Genetic enhancement Genetic Vectors Human artificial chromosome (HAC) Herpes simplex Virus-1 (HSV-1) amplicons Herpesvirus 1 Human Human artificial chromosome Computational biology Gene delivery Biology medicine.disease_cause Genome Article Chromosomes Artificial Human 03 medical and health sciences chemistry.chemical_compound Gene therapy 0302 clinical medicine medicine Humans Gene Gene Transfer Techniques Genetic Therapy Cell Biology Amplicon 030104 developmental biology Herpes simplex virus chemistry Multigene delivery 030220 oncology & carcinogenesis HPRT gene expression DNA |
| Zdroj: | Experimental Cell Research |
| ISSN: | 0014-4827 |
| Popis: | Gene expression studies and gene therapy require efficient gene delivery into cells. Different technologies by viral and non-viral mechanisms have been used for gene delivery into cells. Small gene vectors transfer across the cell membrane with a relatively high efficiency, but not large genes or entire loci spanning several kilobases, which do not remain intact following introduction. Previously, we developed an efficient delivery system based on herpes virus simplex type 1 (HSV-1) amplicons to transfer large fragments of DNA incorporated in human artificial chromosome (HAC) vectors into the nucleus of human cells. The HSV-1 amplicon lacks the signals for cleavage and replication of its own genome, yet each amplicon has the capacity to incorporate up to 150 kb of exogenous DNA. In this study, we investigated whether the capacity of gene delivery could be increased by simultaneously introducing multiple HSV-1 modified amplicons carrying a gene expressing HAC vector into cells with the aim of generating a single artificial chromosome containing the desired genes. Following co-transduction of two HSV-1 HAC amplicons, artificial chromosomes were successfully generated containing the introduced genes, which were appropriately expressed in different human cell types. |
| Databáze: | OpenAIRE |
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