Technology of genomic balancing of chromatin of autologous hematopoietic stem cells for gene therapy of fatal immune-mediated diseases of civilization, extended life expectancy and sudden human death prevention.
| Autor: | Bryukhovetskiy AS; JSC NeuroVita Clinical Hospital, Moscow, Russia. Electronic address: neurovitaclinic@gmail.com., Grivtsova LY; FGBU MRRC named after A.F. Tsyb - Branch of the FGBU National Medical Research Center for Radiology of the Ministry of Health of Russia, Obninsk, Russia., Bogachev SS; Institute of Cytology and Genetics of the Russian Academy of Sciences, Novosibirsk, Russia., Ustyugov AA; Research Institute of Biologically Active Substances of the Russian Academy of Sciences, Chernogolovka, Russia., Nebogatikov VO; Research Institute of Biologically Active Substances of the Russian Academy of Sciences, Chernogolovka, Russia., Shurdov MA; JSC NeuroVita Clinical Hospital, Moscow, Russia. |
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| Jazyk: | angličtina |
| Zdroj: | International review of neurobiology [Int Rev Neurobiol] 2023; Vol. 172, pp. 237-284. Date of Electronic Publication: 2023 Sep 26. |
| DOI: | 10.1016/bs.irn.2023.07.005 |
| Abstrakt: | A biotechnology for personalized ex vivo gene therapy based on molecular genomic balancing of hematopoietic stem cell (HSC) chromatin with nucleosome monomers of human genomic DNA (hDNA nmr ) has been developed and implemented in the clinic to change (to "correct") mutant chromosome loci genomes of dominant HSC clones that form mono- and oligoclonal hematopoiesis during aging and major (oncological, cardiovascular, neurodegenerative and autoimmune) fatal immune-mediated diseases of civilization. A fundamentally new biotechnological approach has been applied to the delivery of genetic material into eukaryotic stem and progenitor cells by establishing an artificial "recombinogenic situation" in them to induce homologous recombination (equivalent replacement) of mutant DNA regions with healthy hDNA nmr . In experimental preclinical trials, the effectiveness of genomic balancing technology has been proven to reduce the risk of sudden death in old animals and to increase the lifespan of outbred mice by 30% and Wistar rats by 57%. The improvement in their quality of life, compared with the control, is explained by an increase in the telomeric regions of the HSCs and HPCs chromosomes by 1.5-2 times. The potential of the technology to slow down the hereditary neurodegenerative diseases on the model of amyotrophic lateral sclerosis is shown. The effectiveness of this technology in clinical practice is presented on the example of a terminal patient with stage 4 neuroendocrine cancer. This technology used in the treatment of a number of oncological, neurodegenerative, autoimmune and hereditary diseases with clonal hematopoiesis is able to arrest the progression of the disease, prevent its recurrence, prolong the active life of a person, increase the average life expectancy and prevent sudden death. (Copyright © 2023. Published by Elsevier Inc.) |
| Databáze: | MEDLINE |
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