Module 8 : GENE THERAPY : INTRODUCTION AND METHODS

Lecture 1 : Gene Therapy: Introduction and Methods

•  Other Viral Vectors:

These include herpes simplex virus vectors and baculovirus.

Herpes simplex virus vectors : Herpes simplex virus-1 (HSV-1) is a 150 kb double-stranded DNA virus with a broad host range that can infect both dividing and non-dividing cells. the insert size is comparatively larger (>20kb) but have a disadvantage of short-term expression due to its inability to integrate into the host chromosome

Baculovirus: They can take up very large genes and express them highly efficiently. They help in recombinant protein expression in insect cell. They can infect hepatocytes as an only mammalian cell type and the gene expresses under the control of either mammalian or viral promoter.

Simian Virus 40 Vectors (SV40): SV40 is icosahedral papovavirus with a circular double stranded DNA of 5.2kb size as genetic material. The genome encodes for early proteins viz; large T antigen (Tag) and small t antigen (tag) and late protein viz; a regulatory protein agnoprotein and three structural proteins (VP1, VP2, VP3). The Tag gene is removed as it is responsible for inducing immunogenicity in the recombinant SV40 vector. All the structural proteins except the major capsid protein VP1 is removed resulting in a genome of 0.5kb size which includes origin of replication (ori) and encapsidation sequence. Recombinant SV40 vectors allows expression of transduced gene

8-1.7.2 Non- viral vectors

It involves chemical and physical methods such as direct injection of naked plasmid DNA (particle bombardment), receptor-mediated endocytosis and gene transfer through liposomes, polymers, nano particles etc.