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Product Details


Product: s50

Manufacturer: GeneSegues

Product page: (external link)

Product Sector: Medical → Drug Delivery



GeneSegues' sub-50 nanometer (s50) capsules function as "synthetic phages" to overcome the series of biological barriers which block administered RNA interference (RNAi) therapies from reaching and engaging their intracellular target.

The Technology Need

50 nanometers (nm) is an important biology threshold that influences a particle's ability to exit the bloodstream, penetrate tissue, and avoid intracellular endosomes. Most competitive RNAi delivery particles including liposomes are larger than 50 nm diameter, a structural disadvantage for addressing RNAi's collective delivery barriers.

In limited applications, larger particles are able to reach target cells due to unique pathophysiological characteristics of the target and its environment. For example, larger particles are known to reach the perimeter cells of solid tumors due to the 'leaky vasculature' that characterizes tumor bloodstream. However, these particles are typically unable to uniformly disperse to the interior cells of solid tumors. Further, for those perimeter tumor cells that larger particles do reach, uptake is most often via the clathrin path, a degradative pathway found in all cell types, inevitably resulting in endosomal capture that (a) will degrade the drug unless early escape is achieved, and (b) regardless of escape success, will potentially trigger the immune-system activators that reside in the endosomes.

s50 Capsule Technology

s50 capsules by virtue of their size and structure efficiently exit the bloodstream and uniformly penetrate tissue, including tumor mass. Further, 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 the clathrin-mediated fate of endosomal capture and its related degradative and inflammatory mechanisms.

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 RNAi delivery has been demonstrated to produce target knockdown and phenotypic benefit at low dosages in primary and disseminated tumor models, as well as in other in vivo indications.

s50 capsules are prepared by encapsulating the drug cargo (including single or double strand RNAi molecules, or plasmids) in a crystalline shell consisting of the targeting moiety, such as proteins or peptides. This efficient, noncovalent design produces a neutral-charge, stable, drug-shielding, targeted vehicle that is typically 10-20 nanometers in diameter, with payload accounting for approximately 70% of the capsule weight. Competitive technologies normally add components to achieve neutral charge, stability, and targeting, thus increasing size, decreasing payload weight percentage (to ~10-20%), and adding manufacturing complexity. Thus, s50 technology provides significant advantages in terms of RNAi therapy efficacy, scalable production, and cost efficiency.

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