[Zinc finger proteins: tools for site-specific correction or modification of the genome].
The ability to achieve site-specific correction or modification of the genome has widespread implications for basic and applied research. Individual zinc finger (ZF) domain recognizes DNA triplets with high specificity and affinity. They are used to create zinc finger protein (ZFP), like the ZF-nucleases, which could be designed to be specific for nearly any site in the genome. These domains can be tandemly linked to recognize DNA sequences of different lengths, with high fidelity. Different methods have been developed to design ZF specifically targeted to any triplet. This modular design offers a large number of combinatorial possibilities for the specific recognition of DNA. By fusing ZF to repression or activation domains, genes can be selectively targeted and switched off and on. Zinc-finger proteins (ZFPs) that recognize novel DNA sequences are the basis of a powerful technology platform with many uses in therapeutics. The ZF have been used as the DNA-binding domains of novel transcription factors (ZFP TFs) which are used to inhibit or activate genes involved in different diseases. ZF-nucleases are developed to modify genes implicated in different diseases. Many clinical trials using ZFPs are currently under investigation.
Dion
Sarah
S
Laboratoire d'Etude des Parasites Génétiques, FRE CNRS 2969, Université François Rabelais, Parc Grandmont, 37270 Tours, France. sarah.dion@etu.univ-tours.fr
Demattéi
Marie-Véronique
MV
Renault
Sylvaine
S
D020816:Amino Acid Motifs; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D015894:Genome, Human; D006801:Humans; D008957:Models, Genetic; D016254:Mutagenesis, Insertional; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D052416:Targeted Gene Repair / Q000379:methods*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D016335:Zinc Fingers / Q000502:physiology*
D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D004247:DNA