TECHNOLOGY PLATFORM

The opportunity
50 nanometers (nm) is an important biology threshold that influences a particle’s ability to exit the bloodstream, penetrate tissue, and avoid intracellular endosomes that destroy invading molecules. With regard to topical applications, small size is also critical for penetrating the thick stratum corneum layer of the skin. Most competitive nucleic acid delivery particles including liposomes are larger than 50 nm in diameter, a structural disadvantage for addressing nucleic acid’s collective delivery barriers.

s50 novel pharmacology
s50 capsules by virtue of their size and structure efficiently exit the bloodstream and uniformly penetrate tissue. s50 capsules have also been demonstrated to deliver nucleic acid cargo to target cells across the skin barrier after passive topical application. Further, upon entering target cells, s50 capsules and their cargo avoid endosomes, which is inherently preferable to attempting to escape from endosomes. Endosomal-avoidance is achieved by co-opting the size-sensitive lipid raft (aka ‘caveolar’) pathway of the target cell, avoiding endosomal capture and its related degradative and inflammatory mechanisms that are the fate of competing delivery technologies.

In these respects, s50 capsules function as synthetic phages, mimicking the effective pharmacokinetic capabilities of natural viruses - most particularly, the nonimmunogenic SV40 virus. Consequently, s50-mediated nucleic acid delivery has been demonstrated to produce phenotypic benefit at low dosages in vivo , including in tumor and liver disease models.

s50 novel process
s50 capsules are prepared by encapsulating the vaccine or drug cargo in a crystalline shell consisting of the desired targeting moiety, such as proteins or peptides. This efficient, noncovalent design produces a neutral-charge, stable, drug-shielding, targeted vehicle that is typically 10-30 nanometers in diameter, with payload accounting for approximately 70% of total capsule weight. Competitive technologies typically add components in efforts to achieve neutral charge, stability, and targeting, thus increasing size, decreasing payload weight percentage (to ~10-20%), and adding manufacturing complexity - and are still relegated to endosomal capture. Thus, the s50 technology platform provides significant advantages in terms of nucleic acid therapy functional delivery, scalable production, and cost efficiency.

©2011 GeneSegues, Inc.