SiSaf exercises its option under licencing agreement on gene therapy for rare bone disease

Guildford, UK

4 November 2021

SiSaf exercises its option under licencing agreement on gene therapy for rare bone disease and announces progress on IND enabling studies

  • SiSaf has exercised its option under its research collaboration and licensing agreement with the University of L’Aquila, Italy
  • Developing small interfering RNA (siRNA) treatment for the debilitating and untreatable bone disease, Autosomal Dominant Osteopetrosis Type 2 (ADO2), enabled with its’ proprietary Bio-Courier®technology
  • Advantages of Bio-Courier, next generation silicon stabilized hybrid lipid nanoparticles (sshLNP), confirmed with positive phenotypic changes observed in pre-clinical studies
  • IND to be submitted by Q1 2024, with Phase I trial to be led by Indiana State University Medical School

SiSaf Ltd, a company developing RNA therapeutics for rare genetic skeletal disorders, today announced that it has exercised its option under its collaboration with the University of L’Aquila, Italy. The license enables SiSaf to develop small interfering RNA (siRNA) targeted via its Bio-Courier® next generation silicon stabilized hybrid lipid nanoparticles (sshLNP) to regulate the expression of a mutant gene expressed by osteoclasts and other cell types responsible for causing the therapeutically neglected rare autosomal dominant disorder type 2 Osteopetrosis (ADO2) in adults.

SiSaf and the University of L’Aquila entered into the research collaboration and licensing agreement last year. The exercise of its option follows 12-months intensive pre-clinical collaborative research between the parties to demonstrate that Bio-Courier targeting addresses the drawbacks seen with viral vectors that has been the current standard in gene therapy delivery to date.

Specifically, results from the pre-clinical studies demonstrated that SiS-101-ADO2, an ADO2-specific siRNA combined with SiSaf’s Bio-Courier platform, downregulates the expression of the mutant CLCN7 gene and rescues bone mass and quality to nearly normal levels. The treatment was well tolerated, inducing no adverse events.

SISaf is now committed to developing SiS-101-ADO2 for the treatment of autosomal dominant osteopetrosis type 2 and is preparing data for its IND package with the aim of submitting an application to the US FDA by Q1 2024. Given the urgent medical need in autosomal dominant osteopetrosis type 2 patients and the lack of any existing therapies, SiSaf intends to file for Orphan Drug Designation for its therapy.

“The translation of positive pre-clinical results into a clinical reality has been impeded by the requirement to repeatedly eliminate the mutant copy of the mRNA without affecting the healthy copy, a challenge in all autosomal dominant disorders” said Professor Anna Maria Teti leader of the team at the University of L’Aquila and recognised leaders in genetic bone disorders.

Professor Teti’s team had demonstrated that a siRNA-based experimental treatment for adult Osteopetrosis type 2 is feasible in human cells and transgenic mice (1).  Further, the study suggested that similar strategies could be applied to other autosomal dominant bone diseases, opening an avenue for wider use of RNA interference therapy in rare genetic disorders.

“The formulation of an ADO2-specific siRNA with SiSaf’s Bio-Courier next generation sshLNP technology has enabled repeated safe systemic administration, sufficiently stabilizing and protecting the siRNA in the circulatory system to demonstrate sustainable transfection and phenotypic reversion to restore healthy bone architecture” Professor Teti said.

Michael Econs, MD, Distinguished Professor of Medicine and Medical and Molecular Genetics at Indiana State University Medical School and a world-leading expert in metabolic bone disease will lead the planned Phase I clinical study and is supporting the trial design.

Dr Econ’s lab is currently performing translational studies in ADO2 using its mouse model of this disease and has initiated a natural history study in ADO2 patients, which will support endpoint design and study evaluation.

Autosomal dominant osteopetrosis type 2 (ADO2), also known as marble bone disease or Albers-Schönberg disease, affects one in every 20,000 individuals. It is marked by increased bone density due to a defect in bone resorption by osteoclasts, a type of bone cell that breaks down bone tissue. This process is critical to maintaining healthy bone and the defect leads to bone that is brittle and susceptible to fracture, which is often accompanied by bone pain and skeletal abnormalities significantly impairing the patient’s quality of life.  At present, there is no effective medical treatment.

Dr Suzanne Saffie-Siebert, PhD, founder and Chief Executive Officer at SiSaf said, “ADO2 is a severe and debilitating disease for which there is no treatment. We are very encouraged to have made positive progress in demonstrating that our technology can overcome the inherent constraints of both viral delivery systems and lipid nanoparticles, especially in recurrent systemically delivered autosomal dominant disorders, an area with huge potential.

“Our lead programme to substantially alleviate autosomal dominant osteopetrosis type 2 would be life changing for patients with this incurable condition and we are excited to be developing the siRNA therapy towards clinical trials”.

SiSaf has an ongoing collaboration with Professor Teti’s group and is working to extend its pipeline of Bio-Courier targeted siRNA therapies to cure other genetic skeletal disorders. Its strategy is to develop its pipeline of novel therapies through clinical studies and then seek collaborative partnerships with marketing expertise in genetic skeletal disorders and rare diseases.

Ends –


SiSaf is delivering on the promise of RNA therapeutics to transform the treatment of genetic diseases. It has pioneered the development of Bio-Courier®, patented next generation silicon stabilized hybrid lipid nanoparticles (sshLNP) that is safe, effective and accessible. It is using the technology to advance an in-house pipeline of RNA therapeutics for rare genetic skeletal disorders. Its strategy is to work with leading academic groups to identify innovative targets for RNA therapies and with leading clinicians to evaluate human efficacy of its RNA therapeutics.

Being a bioabsorbable silicon-lipid hybrid, Bio-Courier optimises the delivery of gene therapeutics, offering superior stability and protection of its payload and lipids while reducing the potential of adverse immune events.

Founded by entrepreneur and leading biomaterials specialist Dr Suzanne Saffie-Siebert, SiSaf is headquartered in Guildford, UK, with fully integrated state-of-the-art research labs, pilot manufacturing and bioanalytical facilities. SiSaf partners with speciality pharmaceutical companies to maximize the potential applications of its Bio-Courier platform.

SiSaf is a private company supported by venture capital investors including Vickers Venture Partners & UK Future Fund.

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The University of L’Aquila ( is a public body based in the region of Abruzzo, Central Italy. It is globally significant for its research expertise in many disciplines, including medicine and biotechnology. The group headed by Prof Teti is recognised worldwide for their research on bone physiology and pathology, including osteoporosis, bone oncology and the rare genetic bone disease osteopetrosis.


Scius communications (for SiSaf)

Sue Charles –     +44 7968726585

Katja Stout –     +44 7789435990