[Targeted Genome Editing With Engineered Nucleases- a New Approach in Gene Therapy]

Nowadays, targeted genome engineering is one of the most important advances in genetic engineering. This process is based on the function of engineered endonucleases. These tools can make desirable genetic changes through creating double strand breaks followed by homologous recombination or nonhomologous end joining mechanisms in a specific site on genome. Genome editing endonucleases have strong ability in understanding the gene performance and gene therapy applications. Meganucleases are the first group of these tools which are naturally found in all creatures and play a crucial role in the targeted genome engineering. zinc finger endonucleases [ZFNs] are the second class made using fusion of a series of DNA recognition Zinc finger domains with catalytic domain of FokI enzyme. Another class of these nucleases includes Transcription activator like-effector nucleases [TALENs] in which, DNA recognition domains are derivatives of transcription activator like-effector proteins from Xanthomonas species, plant pathogen bacteria? fused with catalytic domain of FokI enzyme, like previous class. The last class of these engineered endonucleases, modeled on bacterial adaptive immune system which are called CRISPR/Cas. In this system, Cas9 endonuclease is recruited to the target sequence by a guide RNA that pairs with target DNA and then the enzyme cuts the DNA. In this review, characteristics of the four endonucleases mentioned above and some advances in this area for enhancing its efficiency and specificity in basic and practical researches will discuss through personal experiences and up to date references.