BIOLOGICAL PLATFORM FOR NUCLEIC ACID AND GENE EDITING DELIVERY

SiVEC is focused on developing a drug delivery platform that is characterized as nonpathogenic bacteria that constitutively generate therapeutic nucleic acids and gene editing components for targeted intracellular delivery to mucosal epithelial cells.

PROBLEM

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.

SOLUTION

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.     

         

COMPETITIVE ADVANTAGES

SiVEC’s bacterial delivery platform has several competitive advantages over viral
vectors and lipid nanoparticles. Unlike these other systems whose safety is
compromised because they are highly immunogenic, our delivery system has been
engineered to avoid immune recognition and can be used for repeat dosing. Our
system can safely target a wide range of tissues and tumors that are inaccessible
using these traditional delivery systems. And because our bugs are not cleared by
the liver, toxicity is a non-issue. Unlike even the best viral vectors which are limited
to a 4 kb payload, our system can generate and deliver nucleic acid cocktails that
are well over 10 kb in size. This all relates back to a large therapeutic window,
meaning you can reach an effective therapeutic dose using our system without
unacceptable adverse events. Finally, because our bugs produce the nucleic acids,
this system provides a distinct advantage by eliminating the cost of RNA
manufacturing.

THERAPEUTIC APPLICATIONS

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.