Controlling the kinetics of transgene expression by plasmid design.

Abstract:

:While a vast array of liposomes, peptides, and molecular conjugates have been evaluated for nonviral gene transfer, the entity containing the actual gene itself is almost always a plasmid. The layout of most plasmid DNA (pDNA) vectors is usually quite simple, consisting of a promoter, transgene, polyadenylation signal, and a backbone that permits propagation of the plasmid in bacteria. Additional sequence elements and modifications can be incorporated to influence the stability of gene expression and retention of the pDNA molecule in a given tissue. This review describes the different choices that can be made when designing a pDNA vector for transient, sustained, or regulated expression. The choice of promoter is a major determinant governing the kinetics of expression, but other factors, such as CpG content and the topological form of the pDNA are also influential. Vectors can also be designed to respond to the local environment of a given cell or tissue, or engineered to respond to a small molecule drug.

journal_name

Adv Drug Deliv Rev

authors

Yew NS

doi

10.1016/j.addr.2004.12.009

subject

Has Abstract

pub_date

2005-04-05 00:00:00

pages

769-80

issue

5

eissn

0169-409X

issn

1872-8294

pii

S0169-409X(05)00010-4

journal_volume

57

pub_type

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