The lack of efficacious and universal tools for Systemic Delivery of nucleic acids is widely-recognized as the major factor holding back clinical implementation of genetic drugs. The problem is that nucleic acids such as RNAi are relatively large and carry negative charges; therefore in order to take it across the cell’s membrane, very strong activation energy is required. Aposense’s Molecular Nano-Motors (MNMs) are rationally designed in order to break-down the Systemic Delivery barrier. These MNM are energized by the membrane dipole potential, a recently-discovered voltage, measurable in every leaflet of any phospholipid membrane. Due to the high hydrophobicity of biological membranes, the dipole potential translates into an enormously strong electric field of up to 1 billion V/m (!), spanning ~30 Å, from membrane surface to membrane center.
Fascinated by the fact that every cell harbors its own discrete and strong powerhouse, Aposense developed rationally-designed MNMs (Fig. 1), 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 (Fig. 2), this intra-membrane movement of the MNMs is utilized for the trans-membrane delivery of macro-molecule drugs such as siRNA into the cytoplasm, where they exert their pharmacological effects, e.g., gene silencing.
To date, Aposense conducted extensive biological experiments that have shown that our MNMs can simply and efficiently deliver large, heavily negatively-charged oligonucleotides into cells(Fig. 3), and perform desirable biological actions (e.g., gene silencing). Our delivery system extends widely beyond the liver (Fig. 4), into various other organs (e.g., heart, lung, spleen, kidneys, and lymph nodes).
The MNMs are modular, can be “click attached” to any oligonuleotide sequence. its unique systemic distribution opens broad avenues to address unmet clinical needs and most important the technology is based on Experimentally-validated, novel Mechanism of Action. Aposense MNM mission is to set a novel, unified industry standard, addressing the challenge of trans-membrane delivery of nucleic acids for clinical use, and translating the vision of genetic therapeutics into a “druggable” reality.