Senolytic gene therapy
Numerous research groups using various methodologies have demonstrated that the introduction of cells that have entered the phase of physiological aging into a young organism causes the development of pathologies associated with aging, while the destruction of these cells is able to eliminate these pathologies and increase life expectancy.
Most modern approaches to the development of senolytic (selectively destroying cells that have entered the phase of physiological aging) therapy involve the use of small molecules, peptides and similar compounds. However, such methods are tissue-specific, and their adaptation to other tissues or cells is very difficult or even impossible.
The approach proposed by Oisin Biotechnologies specialists, on the contrary, is a programmable gene therapy. The principle of the approach is to deliver into cells highly specific DNA plasmids that do not integrate into the genome, encoded in which the gene of the enzyme caspase-9 is activated upon contact with the target protein. This triggers the process of programmed cell death, or apoptosis. Non-toxic, charge-free nanoliposomes are used as a carrier of plasmids, which, with the help of a fusion protein, deliver plasmids directly into the cytoplasm of target cells.
This method allows selectively destroying cells expressing a particular target protein. Currently, the developers are working on the proteins p53 and p16, as they are the main markers of cancer and aging cells. As new information about the physiological aging of cells becomes available, the approach can be adapted to any target proteins.
To date, the preclinical study conducted by the developers on mice has been going on for more than 6 months. In order to save time and money, normally aging animals aged 2 years (106 weeks) were included in it. The mice were divided into a control group receiving injections of phosphate buffer solution (PBS) and 3 experimental groups receiving therapy against p16, p53 or a combination of these two proteins. All injections were carried out once a month before the death of the animals, the dose of the experimental drug administered was 4 mg per kg of body weight.
As a result, the best survival results were demonstrated by animals of the combination therapy group. The research is ongoing.
More detailed information about the results of this and other studies of Oisin Biotechnologies can be found in the presentation of John Lewis Selective Ablation of Senescent and Malignant Cells Using Apoptotic Gene Therapy, presented at the congress of the International Association for the Study of Physiological Cell Aging held on July 8-11 in Montreal.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru Based on the materials of Fight Aging!: Oisin Biotechnologies Produces Impressive Mouse Life Span Data from an Ongoing Study of Senescent Cell Clearance.