Herpes simplex virus type-1 HSV amplicon vector construction methods and reviews
Targeting HSV amplicon vectors (method)
An original technique article on HSV vector construction by Grandi and Wang etc.
Targeting HSV amplicon vectors. Methods. 2004 Jun;33(2):179-86.
Abstract:
Several techniques have been developed to deliver DNA directly into mammalian cells, spanning in di?culty from simple mixing procedures to complex systems requiring expensive equipment. Viral vectors have proven able to deliver genes into mammalian cells with high e?ciency and low toxicity. In particular, herpes simplex virus type-1 (HSV-1) amplicon vectors are well suited for gene transfer studies as they can infect many cell types, both non-dividing and dividing, have a large transgene capacity and are easy to manipulate. For some applications, it may be desirable to target gene delivery to speci?c cell populations or to transduce normally non-susceptible cells. This can be achieved by modifying one or more of the glycoproteins found in the viral envelope. Glycoprotein C (gC) has a well-characterized heparan sulfate binding domain (HSBD) necessary for HSV binding to cells. Replacing this region with unique ligands can result in less e?cient binding to natural target cells and increase binding to cells which express receptors for these ligands. A method to retarget amplicon vectors by replacing gC HSBD with a model ligand, the hexameric histidine-tag, is described, as well as means to evaluate the binding of modi?ed vector as compared to wild-type virus to cells with or without the appropriate receptor, in this case, a his-tag pseudo-receptor. This protocol demonstrates increased binding of modi?ed virus to receptor-positive cells (at levels greater than wild-type) with no loss of infectivity. Retargeted vectors can provide an additional tool for increasing the e?ciency of gene delivery to speci?c cell types.
Herpes simplex virus-based vectors (by Lachmann R.)
International Journal of Experimental Pathology. 2004 Oct;85(4):177-90.
Herpes simplex virus (HSV)-based vectors have primarily been developed for neuronal gene delivery, taking advantage of the virus' natural neurotropism. Two types of vector are available: replication defective viruses, whose cytotoxicity has been abolished by deleting viral gene products, and amplicon vectors, which are plasmids packaged into HSV particles with the aid of a helper virus. In this review I discuss how the cytotoxicity of the wild-type virus has been abolished, the progress which has been made toward defining promoter elements capable of directing long-term transgene expression form the latent viral genome and some of the potential clinical uses of these versatile vectors.
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