The human genome is comprised of approximately 22,000 genes, each embodied as a region of deoxyribonucleic acid (DNA) that contains codes for the synthesis of certain proteins.
DNA, which consists of building blocks known as “nucleotides,” occurs in the familiar “double helix” shape, with two strands coiled around the same axis. One end of a chain of DNA is known as the three prime (3’) end, while the other is called the five prime (5’) end. The process by which a cell makes a protein involves two steps, transcription and translation. When a gene coding for a particular protein becomes active within a cell, the two strands of DNA for that gene unwind. During transcription, the cell reads the code in one DNA strand and produces a single-stranded chain of ribonucleic acid (RNA) called messenger RNA (mRNA), which contains the code to produce the protein. During translation, the cell reads the code in the mRNA strand and produces the protein.
During RNA interference (RNAi), a form of double-stranded RNA (dsRNA) is introduced into a cell. Since RNA is typically single-stranded, this double-stranded form triggers the destruction of the dsRNA and any mRNA having a substantially similar genetic code. Once an mRNA strand is destroyed, it cannot be translated into a protein. This effectively “silences” the gene that codes for that protein and prevents it from promoting disease. The process of gene silencing has potential therapeutic value because it provides a defense against viral infections and other diseases.
RNAi (a 2006 Nobel Prize-winning discovery), which functions across a wide range of plants and animals, is a useful laboratory tool for the study of gene function.
Health Impact
In 2018, The U.S. Food and Drug Administration (FDA) approved Onpattro (patisiran) infusion for the treatment of peripheral nerve disease (polyneuropathy) caused by hereditary transthyretin-mediated amyloidosis (hATTR) in adult patients. This is the first FDA-approved treatment for patients with polyneuropathy caused by hATTR, a rare, debilitating and often fatal genetic disease characterized by the buildup of abnormal amyloid protein in peripheral nerves, the heart and other organs. It is also the first FDA approval of a new class of drugs called small interfering ribonucleic acid (siRNA) treatment.
Sirnaomics, Inc.
Sirnaomics is a clinical stage biopharmaceutical company specialized in RNAi-based therapeutics for addressing the unmet needs in treatment of cancers and fibrosis diseases. The company has developed proprietary polypeptide nanoparticle carriers for efficient siRNA delivery, to advance an enriched drug product pipeline.
Sirnaomics’ lead product candidate, STP705, is an siRNA (small interfering RNA) therapeutic which takes advantage of a dual-targeted inhibitory property together with a polypeptide nanoparticle (PNP)-enhanced delivery to directly knock down both TGF-β1 and COX-2 gene expression. The product candidate has received multiple IND approvals from both the US FDA and Chinese NMPA, including treatments of Cholangiocarcinoma, Non-Melanoma skin cancer and Hypertrophic Scar. STP705 has also received Orphan Drug Designation for treatment of Cholangiocarcinoma, Primary Sclerosing Cholangitis and Hepatocellular Carcinoma. A recent interim analysis report of a phase IIa clinical study on STP705 for treatment of Squamous Cell Carcinoma in situ indicated the topline therapeutic results with complete histological clearance tumor cell on treated sites. Using the same dual targets design, Sirnaomics has further developed STP707, a systemic formulation with broader application potential.