BIOLOGICAL PLATFORM FOR NUCLEIC ACID DELIVERY
SiVEC is focused on developing a drug delivery platform that is characterized as nonpathogenic bacteria that constitutively generate therapeutic nucleic acids for targeted intracellular delivery to mucosal epithelial cells.
Nucleic acid (NA) therapeutics have great potential to revolutionize human medicine. However, a major barrier to their widespread potential is the lack of efficient delivery vehicles to clinically relevant tissues. This biological barrier requires systemic and high doses of NAs, often utilizing complex chemical modifications, use of integrative viral vectors, synthetic carriers, nanoparticles, and other ligands to attain clinical efficacy and site-specific delivery. There are many safety and production limitations for clinical use including toxicity, practicality, biocompatibility, stability, and manufacturing costs.
SiVEC is focused on developing a drug delivery platform that is characterized by nonpathogenic bacteria that constitutively generate therapeutic nucleic acids for targeted intracellular delivery to mucosal epithelial cells without genomic integration. This platform theoretically overcomes challenges with delivery to specific cells and tissues, particularly the eyes, respiratory, vaginal/genital and gastrointestinal tissues. This biological NA delivery platform has been well validated as a vehicle to generate and deliver short hairpin RNA (shRNA) to mucosal epithelial tissues including respiratory tissues.
This non-viral delivery platform is naturally derived, engineered to be non-pathogenic, non-immunogenic, and is further characterized as having a high delivery efficiency for targeted NA delivery to specific tissues, good biocompatibility, and can be administered using a wide range of delivery routes without systemic adsorption.
Our NA delivery vehicle is naturally derived but specifically engineered to overcome the multitude of issues associated with other delivery options such as liposomes, synthetic vehicles, viral vectors, ligands, and the bacterial-mediated delivery of plasmid DNA (bactofection). Compared to prior state-of-art delivery platforms, our delivery vehicles are characterized as uniquely: 1) Non-pathogenic due to an engineered amino acid deletion, preventing replication and viability outside of a supplemented medium; 2) Not recognized by the innate immune system (antigen presenting cells - APCs); 3) Able to specifically target cells in a sequence-independent manner and be taken up intracellularly; 4) Able to escape the host cell endosome and release their NA payload into the cytosol for processing or nuclear translocation; 5) Constitutively generate NAs from an expression cassette for maximum payload delivery; 6) Allow for controlled and safe delivery of NAs by avoiding gene integration into the host tissues; 7) Fast-acting due to delivery of pre-generated NAs directly to the site of infection, and 8) Ease of production and low manufacturing costs.
Our biological delivery vehicle could be used therapeutically to provide targeted delivery of stable NAs to important sites of disease throughout the body. The mucosal epithelial surfaces where pathogens and allergens are most likely to invade the body are also the surfaces that our delivery vehicle targets, making targeted and specific delivery a very attractive treatment option using our biological delivery platform.
A wide range of important bacterial and viral diseases are transmitted via mucosal tissues such as the mouth, eyes, nose, lungs, stomach and intestines, vagina, and rectum. Additionally, a wide range of mucosal epithelial tissues are sites of chronic, non-infectious diseases.
These tissues represent sites of delivery with our biological NA delivery platform. This platform has the potential to generate and specifically deliver a wide range and multitude of NA drugs, including small interfering RNA (siRNA), microRNA, microRNA antagonists, aptamers, mRNA, splice-switching and antisense oligos.
This delivery platform is specially engineered to target mucosal epithelial tissues, eliminating the need for exogenous reagents, synthetic peptides, ligands, or chemical modifications. This biological NA delivery platform could provide a breakthrough in the field of NA therapeutics and has tremendous potential as a marketable technology capable of addressing a vast number of therapeutic needs affecting ocular and pulmonary tissues.