Zinc finger proteins are exotically named naturally occurring proteins that can be engineered to encourage a cell to repair genetic mutations. They offer an alternative approach to gene therapy which uses the introduction of a desired gene to correct molecular faults.
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What are Zinc Finger Proteins?
Zinc finger proteins are present in great numbers in eukaryotic organisms. They are DNA-binding protein domains and proteins containing zinc finger regions can bind to DNA, RNA, other proteins, as well as a host of other molecules. They are involved in a range of cellular activities such as transcription, protein folding, RNA packaging, DNA recognition, and regulation of cell death. Specially engineered zinc finger proteins are being used by scientists for applications in genetic engineering.
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How Can Zinc Finger Proteins be used in Gene Therapy?
Zinc finger proteins can be engineered to induce double-stranded DNA breaks in specific DNA sequences, for example where a disease-causing bad gene is located - and then the cell's own repair machinery will go to work to correct the damage.
This offers a way of correcting genetic mutations without resorting to the traditional gene therapy approach which involves housing a desired gene in a vector and then sending it on its way into a body, with fingers crossed that it reaches its target and is then expressed in a way that is required.
How does it work?
The zinc finger DNA-binding domain is fused to the cleavage domain of the Fokl restriction endonuclease, and the complex is called a zinc finger nuclease which can induce the double-stranded breaks in specific DNA sequences.
The zinc finger portion identifies and binds to the DNA, and the cleavage domain chops the genetic sequence. The cellular repair machinery then makes good the damage, with a DNA template supplied by the scientists. The technology can also be used to stop the over expression of genes that may be contributing to a particular disease process.
According to the Zinc Finger Consortium the DNA-binding specificities of any DNA-binding domain can be engineered to target nearly all kinds of genetic sequences.
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What is the Zinc Finger Consortium?
The Zinc Finger Consortium was set up by Daniel Voytas of the University of Minnesota, and J.Keith Joung of Harvard University. Its aim is to "ensure and to promote continued research and development of engineered zinc finger technology." To this end they have created pools of zinc fingers which they make available to other researchers at an affordable cost.