Enhanced expression of recombinant dystrophin following intramuscular injection of Epstein–Barr virus (EBV)-based mini-chromosome vectors in mdx mice

Abstract

Gene transfer by direct intramuscular injection of naked myotube cultures. Intramuscular injection of EBV-based plasmid DNA has been shown to be a safe, simple but dystrophin expression plasmids into nude/mdx mice relatively inefficient method for gene delivery in vivo. Eukaresulted in significant enhancement in the number of musryotic plasmid expression vectors incorporating the cle fibres expressing recombinant dystrophin compared Epstein-Barr virus (EBV) origin of replication (oriP) and with a conventional vector. This effect was observed for EBNA1 gene have been shown to act as autonomous epiover 10 weeks after a single administration. These results somally replicating gene transfer vectors which additionally indicate the potential advantage of EBV-based expression provide nuclear matrix retention functions. Prolonged vectors for focal plasmid-mediated gene augmentation expression of a LacZ reporter gene and recombinant therapy in Duchenne muscular dystrophy (DMD) and a human dystrophin was shown using EBV-based plasmid range of other gene therapeutic applications. vectors transfected into C2C12 mouse myoblast and

LCR-mediated, long-term tissue-specific gene expression within replicating episomal plasmid and cosmid vectors

“…1,[3][4][5]27 In addition to improving the efficiency of REV delivery, advances in two areas need to be made in order for the utility of this system to be realised: episome maintenance and regulated gene expression. The majority of studies addressing gene expression from within REVs, have focused on the use of ubiquitously acting classical promoter-enhancer combinations, such as those from RSV 28 and CMV.…”

“…Lastly, REVs are introduced into the target cells using nonviral delivery systems that can be produced more cheaply at scale than with viral vectors. [3][4][5] REVs based on viral origins of replication such as those from EBV, 6 human papovavirus BK, 7,8 mammalian chromosomal origins of replication have also been found to improve nuclear retention of the episomes. 11,12 It has been demonstrated that both non-replicating, transiently transfected plasmids, 13,14 as well as REVs, 13,15,16 assemble nucleosomes.…”

Non-viral gene delivery in skeletal muscle: a protein factory

“…Several genetically modified viruses, such as retrovirus, herpes simplex virus, Epstein-Barr virus, adenovirus (AdV) and adeno-associated virus (AAV), have all been tested for gene delivery into muscle. [2][3][4][5] Of these, AdV and AAV have been found to be most efficient so far for transducing muscle fibres. [6][7][8] AAV in particular is able to transfect non-proliferating muscle fibres and is considered to be non-pathogenic, as it is not found to be associated with any disease.…”

Viral vectors for gene delivery and gene therapy within the endocrine system

“…This constraint has favoured the use of viral vectors for gene delivery, rather than non-viral systems such as naked DNA-or liposome-mediated gene transfer. Recent developments have made possible enhanced and sustained transgene expression from Epstein-Barr Virus (EBV)-based mini-chromosome vectors (Saeki et al 1998b, Tsukamoto et al 1999.…”