quantity of full length mRNA to quantity of the delta 7 mRNA was over 41 for nusinersen in SNA format compared to 2.3 for nusinersen in the linear format.
Nusinersen in the SNA format significantly increases the levels of stable variant of SMN2 compared to the linear format as measured by changes in mRNA levels in cells derived from SMA patients.
We believe these results suggest that nucleic acid therapeutics based on SNA may have superior pharmacodynamic properties compared to those in the linear format, some of which are already approved by the FDA. The results also suggest that our SNA technology may have applications in a broad range of genetic disorders.
Ophthalmic therapies, such as antibodies, peptides or aptamers, are typically injected into the eye to reach their target tissues and achieve therapeutic effects. We believe that the penetration properties of the SNA may result in the delivery of therapeutically relevant concentrations of oligonucleotides to certain tissues in the eye after topical administration in the form of eyedrops.
To assess penetration into the eye, Dutch belted rabbits were given either eyedrops containing no SNAs, referred to as vehicle, or an SNA in a formulation targeting an ocular gene of interest. The eyedrops were administered to the animals 18 times over the course of five days. On the fifth day, the rabbit eyes were analyzed for SNA content. The results indicate that SNAs were detected in tissues at the surface of the eye, where the application occurred, but also in the retina and vitreous humor, indicating that the SNA had penetrated into the eye.