Jay Sarkar, Turn Biotechnologies - Transient mRNA Reprogramming for Reversal of Cellular Aging Phenotypes

Age-related diseases greatly tax both the healthcare system and the affected elderly. These conditions are generally not curable and are commonly addressed by different specialists, only adding to the societal burden. We have developed a transformative approach to the treatment of age-related disease that focuses on repairing the upstream multi-tiered structure that controls DNA expression, the epigenome. Over time, errors arise in the epigenome that compound on each other, leading to pathway degradation and faulty cellular functioning. With transient exposure to cellular reprogramming factors, we can return the aged epigenome to a more youthful tone, improving cellular function and reducing the hallmarks of aging. This therapy, called the Epigenetic Reprogramming of Aging (ERA), utilizes messenger RNAs to execute its rejuvenative effects, taking advantage of the numerous benefits of this highly titerable, direct, non-integrative, rapidly adaptable, and nontoxic oligonucleotide modality. ERA is distinct from previous anti-aging/pro-longevity interventions that engage discrete aging pathways, thus it is able to provide a multifaceted age reversal effect at the DNA, metabolic, whole cell, and local environmental levels in a variety of cells and tissues. In general, application of the ERA treatment led to a global transcriptomic transition of  treated . Furthermore, this technology effectively reduces the signs of age-related disease pathology in cultured osteoarthritic chondrocytes, as well as enhances regenerative capacity of aged muscle stem cells such that transplantation into the muscle of aged mice effectively restores youthful strength. Further studies in human immune cells show reduced inflammation. Additionally, in vivo delivery is currently under development for direct therapeutic administration of ERA. As a whole, this technology has the potential to dramatically extend the human healthspan.

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