Positive preclinical data for siRNA therapy for osteopetrosis


RNA therapeutics company SiSaf has published positive safety and efficacy data for its siRNA therapy for Autosomal Dominant Osteopetrosis 2 (ADO2).

The data demonstrate that siRNA complexed with SiSaf’s silicon stabilised hybrid lipid nanoparticles (sshLNP) was able to significantly downregulate expression of an ADO2-specific mutant gene.

The company says these results could have significant translational impact on bone disease therapies and open the path to human trials of it’s potentially curative treatment for ADO2.

There are currently no approved treatments for this disease and no other treatments currently in clinical trials.

SIS-101-ADO is an ADO2-specific siRNA specifically designed against the human CLCN7G215R mRNA. When tested via single intraperitoneal injection in pre-puberal ADO2 mice, carrying a heterozygous mutation of the Clcn7 gene (Clcn7G213R), SIS-101-ADO significantly downregulated the Clcn7G213R related mRNA levels in femurs at 48 h. Confirmatory results were observed at two weeks and four weeks after treatments (three intraperitoneal injections/week), with rescue of the bone phenotype and demonstrating safety.

Co-author on the paper, Dr Suzanne Saffie-Siebert, CEO of SiSaf, said: “Targeting the bone safely and effectively is a challenge for RNA-based therapies. The in vivo data for our ADO2 treatment show that SiSaf’s silicon stabilised LNPs are able to deliver siRNA to the bone without any side effects. This is an important milestone on the path to clinical trials of SiSaf’s treatment for autosomal dominant Osteopetrosis type 2. And it could have wider translational significance for RNA-based treatments of other skeletal disorders.”

The FDA granted Orphan Drug Designation for SIS-101-ADO in May 2023, as well as Rare Paediatric Disease Designation for the treatment of Autosomal Dominant Osteopetrosis.

Related Articles

Join FREE today and become a member
of Drug Discovery World

Membership includes:

  • Full access to the website including free and gated premium content in news, articles, business, regulatory, cancer research, intelligence and more.
  • Unlimited App access: current and archived digital issues of DDW magazine with search functionality, special in App only content and links to the latest industry news and information.
  • Weekly e-newsletter, a round-up of the most interesting and pertinent industry news and developments.
  • Whitepapers, eBooks and information from trusted third parties.
Join For Free