Short telomeres accelerate age-related disease and hinder regenerative medicine
Telomeres are repetitive DNA sequences that protect the ends of chromosomes but shorten over time due to oxidative damage and incomplete DNA replication. When telomeres become too short, the DNA end is exposed, causing cells to die, senesce, or become cancerous. Short telomeres limit regenerative capacity of cells for cell therapies, tissue engineering, and regenerative medicine and accelerate age-related diseases and conditions.
TeloEX extends telomeres rapidly and transiently
TeloEX is nucleoside-modified mRNA encoding telomerase reverse transcriptase (TERT). Delivery of TeloEX to cells transiently increases telomerase activity (1-2 days), during which telomeres are rapidly extended. After the brief treatment, the extended telomeres resume shortening at their normal rate, important for safety. TeloEX extends telomeres in days by an amount sufficient to reverse over a decade of telomere shortening in vivo. TeloEX treatment increases proliferative capacity of cells in a dose-dependent manner.
Rapid telomere extension
TeloEX extends telomeres in human fibroblasts in 4 days by 0.9 kb. Controls are untreated; vehicle only; and catalytically-inactive TERT mRNA. (Ramunas, 2015).
Dose-dependent increase in cell replicative capacity
Treatment of human fibroblasts with TeloEX increases replicative capacity in a dose-dependent manner.
TeloEX has several advantages for telomere extension:
Fast: One day of TeloEX treatment reverses more than a decade of telomere shortening.
Transient: TeloEX is degraded in 1-2 days, leaving telomeres extended, but not extending.
Non-immortalizing: After treatment, extended telomeres resume shortening at their normal rate.
Hypoimmunogenic: Made of natural RNA.
Dose-dependent: TeloEX provides cells with a finite, tunable increase in proliferative capacity without immortalization.
TeloEX-based telomere extension has applications in:
Clonal expansion of genetically-modified cells (e.g. CRISPR)
Ramunas, J., Yakubov, E., Brady, J. J., Corbel, S. Y., Holbrook, C., Brandt, M, Stein, J., Santiago, J.G., Cooke, J.P. and Blau, H.M. (2015). Transient delivery of modified mRNA encoding TERT rapidly extends telomeres in human cells. The FASEB Journal 29(5):1930-1939 PMC4415018.
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Rejuvenation Technologies Inc. (RTI) was founded by the Stanford University co-inventors of TeloEX-based telomere extension and business experts. RTI is growing and welcomes inquiries from potential new team members.