10072572INDUCE: Development of siRNA-Mergo® therapeutics for lung indications.ClosedCollaborative R&DInnovate UKINDUCE aims to develop and validate Sixfold's RNA therapeutics delivery system, Mergo?, for delivery of (simultaneously developed) short-interfering RNA (siRNA) gene silencing cargo to a specific tissue type (undisclosed). INDUCE brings together multidisciplinary, high-expertise partners with a track record of successful project completion, allowing for both fast scientific progress and commercial advancement. In comparison to small molecules and antibodies, siRNAs can act on a virtually unrestricted choice of otherwise 'undruggable' therapeutic targets, with high potency and specificity, with the potential to treat a range of disease indications \[1\]. Pioneering regulatory approvals of Alnylam's siRNA therapeutics for liver disorders in 2018-2019 \[2\] substantiated clinical and commercial opportunities for such therapies. However, current delivery approaches remain suboptimal (e.g. GalNAc-conjugates, lipid nanoparticles, viral vectors) due to limitations surrounding cell-specific targeting, cargo-loading capacity, high toxicity and complex/expensive manufacturing, highlighting the need for novel formulations to increase addressable disease indications \[3\]. Mergo(r), Sixfold's proprietary delivery system, addresses these challenges through its modular design based around a central RNA nanoscaffold, which can be functionalized with therapeutics/targeting molecules to recognise biomarkers on specific cells of interest, significantly reducing toxic side-effects from the therapeutic in other cells and tissues. Following demonstration of promising technological maturity through _in vitro/in vivo_ results, additional validation of mechanism-of-action for specific tissue types is needed. INDUCE will develop an in-house therapeutic targeted towards a specific extrahepatic tissue, and exploit the versatility of Mergo(r) to improve delivery via specific tissue-targeting. In turn, INDUCE will generate in-house asset(s) whilst speeding candidate development, and act as a preclinical demonstrator for the application of Mergo(r) to target other clinical indications. Mergo(r) holds significant value-capturing potential in the thriving siRNA therapeutics and associated delivery markets, through improved safety, efficacy, and reduced cost-of-goods (particularly compared to viral technologies). Pharmidex's unique expertise in advanced preclinical drug development will enable the generation of a preclinical data-pack for rapid commercialization and clinical advancements via generation of licensing deals. Sixfold's comprehensive IP portfolio and licensing strategy engages the broader biopharmaceutical supply chain, generating diverse benefits to the wider UK life sciences sector. \[1\]Lam\_J.K.W\_et\_al.\__Mol\_Ther\_Nucleic\_Acids_\_2015\_4(9):e252\. \[2\]Debacker\_A.J\_et\_al.\__Mol\_Ther._\_2020\_28(8):1759-1771.\[3\]Payne\_D\__Nature_\_574\_S1\_2019\.