Small interfering RNA (siRNA) therapies represent a new approach to harness a natural biologic pathway called RNA interference (RNAi). Through RNAi, our bodies regulate the production of different proteins. Researchers first discovered RNAi in 1998. The 2006 Nobel Prize for Physiology or Medicine, awarded to Craig Mello and Andrew Fire, recognized RNAi as a major scientific discovery and set the stage for new breakthroughs in medicines by targeting the root cause of diseases. siRNA therapies are widely considered some of the most promising frontiers in drug development today. siRNA acts “upstream” compared with today’s medicines, preventing the production of disease-causing proteins. A simple analogy is that siRNA therapies work by “turning off the faucet” of disease-causing proteins compared with medicines that inactivate disease-causing proteins after they have been produced. siRNA therapies are designed to be highly selective, working precisely at the desired target and minimizing the risk of off-target effects.
While indicating an enormous potential to advance medicine, all these potentially breakthrough genetic drugs, share one major limitation: being built of oligonucleotides, either natural or modified, with their site of action being inside the cell, the cytoplasm or the nucleus, all these therapeutic agents have to pass through the hydrophobic barriers of cell membranes. Indeed, to date, this robust delivery barrier holds back the entire field of genetic therapies, and precludes its implementation as the medical practice of the future.
Aposense solution a Disruptive Technology
Our Innovative Approach is based on an entirely novel mechanism of action, based on the following pivots: (1) The urgent, unmet need for tools for trans-membrane delivery of siRNA. (2) A recently discovered powerful intra-membrane electrostatic field, related to the membrane dipole potential, and its utilization as the source of energy to energize the trans-membrane drug delivery. (3) An innovative Molecular Nano-Motor, rationally designed to “dig” or “mine” energy from the internal membrane electric field, and to convert it into kinetic energy. (4) Utilization of this kinetic energy to energize the trans-membrane delivery of genetic cargo, such as siRNA into the cell.
Aposense developed rationally-designed Molecular Nano-Motors (MNMs), being novel small-molecule chemical entities, capable of “energy mining” from the internal membrane electric field, and its translation into kinetic energy, for movement within the hydrophobic membrane core. Upon linkage to a cargo drug, this intra membrane movement of the MNMs is utilized for the trans-membrane delivery of siRNA into the cytoplasm, where they exert their pharmacological effects, e.g., gene silencing.
These hallmarks combined with the compact, versatile and modular structure of the MNM, may conceivably quality Aposense’s Gene Delivery Platform to serve as a future unified industry standard for the trans-membrane delivery of genetic drugs.