Site-directed genome modification: nucleic acid and protein modules for targeted integration and gene correction.
A variety of technological advances in recent years have made permanent genetic manipulation of an organism a technical possibility. As the details of natural biological processes for genome modification are elucidated, the enzymes catalyzing these events (transposases, recombinases, integrases and DNA repair enzymes) are being harnessed or modified for the purpose of intentional gene modification. Targeted integration and gene repair can be mediated by the DNA-targeting specificity inherent to a particular enzyme, or rely on user-designed specificities. Integration sites can be defined by using DNA base-pairing or protein-DNA interaction as a means of targeting. This review will describe recent progress in the development of 'user-targetable' systems, particularly highlighting the application of custom DNA-binding proteins or nucleic acid homology to confer specificity.
Kolb
Andreas F
AF
Hannah Research Institute, Hannah Research Park, Ayr, UK, KA6 5HL.
Coates
Craig J
CJ
Kaminski
Joseph M
JM
Summers
James B
JB
Miller
Andrew D
AD
Segal
David J
DJ
D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D018390:Gene Targeting / Q000379:methods*; D024861:Genetic Enhancement / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D023281:Genomics / Q000379:methods*; D016297:Mutagenesis, Site-Directed / Q000235:genetics*; D009696:Nucleic Acids / Q000235:genetics; D015202:Protein Engineering / Q000379:methods*
D004268:DNA-Binding Proteins; D009696:Nucleic Acids