TARGET: RNA nanotechnology delivery platform for gene therapies, towards commercialization in cancer

点击翻译按钮获取中文摘要

TARGET aims to preclinically validate Sixfold's Programmable Oligonucleotide Delivery System (PODS) for delivery of short interfering RNA (siRNA) gene silencing cargo to specific cells. By taking advantage of the interdisciplinary and complementary expertise of the partners --Sixfold and Medicine Discovery Catapult (MDC)-- the project allows for rapid scientific and commercial progress.Compared to small molecule or antibody-based drugs, siRNAs can act on virtually unrestricted choice of --otherwise "undruggable"-- therapeutic targets, with high specificity and potency; while their easy manufacturing allows for rapid lead optimization \[1\]. As such, siRNAs have the potential to provide effective treatment options for a variety of diseases including cancer. The first regulatory approvals of Alnylam's siRNA therapies for liver disorders in 2018-19 \[1-2\] have validated the clinical and commercial opportunity for such therapies. However, the major limiting factor for their further success remains the lack of safe and effective systems for systemic delivery of siRNAs to specific diseased cells \[4\]. Current approaches, primarily GalNAc-conjugates, lipid nanoparticles and viral vectors, are sub-optimal given their limited cell targeting specificity, cargo loading capacity, high toxicity, and complex/expensive manufacturing that limit the type and number of addressable disease indications.PODS can address this drug delivery challenge given their modular design based on a central nanoscaffold, which can be functionalised with therapeutics and targeting molecules that recognise biomarkers on cancer -but not healthy- cells. Sixfold's first-generation PODS demonstrated promising results.TARGET expands PODS utility and creates an intelligent and versatile delivery system that goes beyond the limitations of current standards. As such, PODS represent an attractive opportunity to capture a significant portion of the thriving gene therapy delivery market and could accelerate other Advanced Therapy Medicinal Products (ATMP), through improved safety, efficacy and reduced cost of goods, especially compared to viral technologies. By bringing MDC's unique expertise in advanced preclinical imaging, TARGET allows for completion of a comprehensive preclinical datapack to pharmaceutical industry standards, for rapid commercialization and clinical advancement.Sixfold's broad IP portfolio and business strategy engage the entire biopharmaceutical supply chain, providing diverse benefits to the wider UK life sciences sector.\[1\]Lam\_J.K.W\_et\_al.\_Mol\_Ther\_Nucleic\_Acids\_2015\_4(9):e252.\[2\]Alnylam\_Press\_release\_10\_August\_2018\[3\]Alnylam\_Press\_release\_20\_November\_2019.\[4\]Payne\_D\_Nature\_574\_S1\_2019\.