31 March 2008

Gene therapy with zinc fingers – simple, fast, accurate

Two decades ago, gene therapy was declared a revolutionary method in medicine, but the development of this direction is very slow, there are few achievements, and several patients have already died during clinical trials.

One of the main reasons for this failure is the difficulty of controlling the insertion of therapeutic genes into the patient's chromosomes. When using viral vectors, therapeutic genes are embedded in the chromosomes of infected cells at an arbitrary location, and possible undesirable consequences of this are violations of the structure and functions of existing genes.

Scientists at the University of Cambridge, working under the leadership of the Nobel Prize in Chemistry in 1982, Sir Aaron Klug, have developed a method that allows therapeutic genes to be inserted into a patient's chromosomes with surgical precision using modified "zinc fingers" – zinc-containing proteins that bind to DNA and are one of the main regulators of transcription – reading the genetic code on the matrix RNA. The functioning of these proteins ensures the formation of differences between cells of different types.

Цинковые пальцы связываются только с определенными последовательностями нуклеотидов, что позволяет проводить манипуляции с генами с хирургической точностьюThe authors have developed synthetically versions of these proteins, called zinc-fingered nucleases (zinc-fingered nucleases), which recognize specific DNA sequences, which allows manipulations on specific genes without affecting neighboring DNA sites.

The new method is already undergoing clinical trials organized by the California company Sangamo BioSciences, with the participation of 100 young patients with diabetes complicated by peripheral artery pathology. The tests were initiated after receiving encouraging preliminary results on the use of the method for embedding a gene encoding vascular epithelial growth factor that promotes the restoration of affected vessels.

The next stage of the work is planned to test the method for the treatment of patients with spinal cord injuries.

Targeted gene therapy is also being tested, designed to suppress chronic pain and block the CCR5 gene, due to the interaction with which HIV particles capture T-lymphocytes. This will increase the number of normal T-lymphocytes in the blood of HIV-infected people and thus increase their resistance to both HIV and other infectious agents.

The experimental results also indicate that the new method is also suitable for blocking genes that cause the development of various diseases. This makes it a fundamental technique for animal research.

According to the authors, the main advantage of zinc fingers lies in their simplicity and accuracy in comparison with labor-intensive, long-lasting and often non-reproducible existing methods.

Portal "Eternal youth" www.vechnayamolodost.ru according to the Telegraph


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