Towards Targeted Telomerase Gene Therapy

Interestingly, telomerase upregulation to lengthen telomere length may turn out to be a decent match for the capabilities of lipid nanoparticle (LNP) delivery of messenger RNA (mRNA) as an implementation of gene therapy. This produces one to two days of expression which, by the sound of things, is enough to give telomeres enough of a boost in length to be worth the exercise, can be repeated as needed, is familiar to regulators, and the LNP field is energetically working towards variant LNPs that can target specific tissues and cell types.

The question is whether or not lengthening of telomeres via telomerase gene therapy is a good idea in humans. There is a lot of hype over telomere length, but given that telomeres shorten with each cell division, average telomere length in a tissue is a fuzzy measure of the pace of cell replication versus pace of production of new cells by the stem cells that support that tissue. Stem cell activity declines with age, ergo so does average telomere length. The hypothesized risk lies in extending the life span of cells that are potentially cancerous. In mice, telomerase gene therapy is quite beneficial, both extending life and reducing cancer risk. Humans and other large mammals exhibit very different telomere dynamics, however, so one can't assume that the mouse data is a clear green signal. Given a company working towards this goal, we might hope that questions will be answered in the years ahead.

Longevity biotech Rejuvenation Technologies has emerged from stealth with seed financing to develop mRNA-based therapeutics to address mechanisms of aging. The company says it has developed an mRNA approach "capable of rewinding 10 years of telomere shortening with a single dose." Rejuvenation's products are optimized telomerase mRNA encapsulated in a custom tissue targeted lipid nanoparticle. The company says it plans to expand its operations and bring on additional team members to oversee scale-up manufacturing, clinical operations, and R&D efforts to expand mRNA delivery capabilities to additional organ systems.

"A single dose of our telomerase mRNA reverses years of telomere shortening in hours. Rejuvenation's LNP technology can also deliver mRNA to the lung and liver, and we've shown remarkable efficacy in preclinical models in both liver fibrosis and liver failure."