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

Abstract

The transfer of genetic material into endocrine cells and tissues, both in vitro and in vivo, has been identified as critical for the study of endocrine mechanisms and the future treatment of endocrine disorders. Classical methods of gene transfer, such as transfection, are inefficient and limited mainly to delivery into actively proliferating cells in vitro. The development of viral vector gene delivery systems is beginning to circumvent these initial setbacks. Several kinds of viruses, including retrovirus, adenovirus, adeno-associated virus, and herpes simplex virus, have been manipulated for use in gene transfer and gene therapy applications. As different viral vector systems have their own unique advantages and disadvantages, they each have applications for which they are best suited. This review will discuss viral vector systems that have been used for gene transfer into the endocrine system, and recent developments in viral vector technology that may improve their use for endocrine applications -chimeric vectors, viral vector targeting and transcriptional regulation of transgene expression.

Real-time imaging of gene promoter activity using an adenoviral reporter construct demonstrates transcriptional dynamics in normal anterior pituitary cells

“…Our study thus demonstrates that adenoviral vectors offer a highly efficient route towards studies of real-time gene regulation in normal cells. Adenovirus vectors are characterized by highly efficient gene transfer into target cells, and can transduce a wide range of cell types, including post-mitotic cells (Stone et al 2000). In the case of the pituitary, the efficacy of adenoviral gene transfer has been demonstrated in a number of studies.…”

“…Pioneering studies using microinjection of individual pituitary cells have revealed important information about pituitary gene regulation in relation to endocrine signals (Castano et al 1996, Villalobos et al 1998, but the microinjection procedure is technically difficult and inevitably entails the selection of a small number of cells for any given experiment. In an attempt to develop an alternative approach, with wider application for species in which conventional transgenesis is not yet established, we developed a viral vector to deliver reporter genes efficiently into primary cells , Stone et al 2000. We have used a recombinant adenovirus (RAd) containing a transcription unit in which the luciferase reporter gene is regulated by a 4400 bp PRL gene promoter fragment.…”

Development of Dioctadecyldimethylammonium Bromide/Monoolein Liposomes for Gene Delivery

“…These molecules selfassemble in highly organized structures capable of complexing the genetic material and later releasing it inside the cells. Whereas viruses generally impose issues of mutagenicity and immunogenicity [16,17], polymers such as polyethylenimine (PEI) are known to be highly cytotoxic [18,19]. By exclusion of alternatives, cationic liposomes have emerged as morphology (lipoplex size, charge ratio (+/-), fluidity and structure) for optimal transfection conditions.…”

Hypoxia-inducible VEGF gene delivery to ischemic myocardium using water-soluble lipopolymer

“…However, the clinical applications of virus vectors are limited because of the intrinsic properties of viruses such as immunogenecity, random integration into chromosomal DNA, inefficiency of large preparation, possible oncogenic rearrangement, and the size limit of DNA. 1 Therefore, to apply viral vectors to clinical gene therapy settings, they should be improved in terms of safety. Another approach of somatic gene delivery is to use nonviral carriers.…”