SUMMIT: SiRNAs Utilising Mergo? delivery for post-Myocardial Infarction Treatment

峰会：SiRNA 利用 Mergo？

• 批准号: 10026765
• 金额: $ 85.54万
• 依托单位: SIXFOLD BIOSCIENCE LTD.
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=10026765
• 关键词: SUMMIT; SiRNAs; Utilising; Mergo; delivery

SUMMIT aims to develop and validate Sixfold's oligonucleotide delivery system, Mergo?, for delivery of (simultaneously developed) short-interfering RNA (siRNA) gene silencing cargo to a specific tissue type (undisclosed). SUMMIT combines multidisciplinary partners with highly complementary expertise and experience in delivering successful projects, with rapid scientific and commercial progress towards early-stage R&D collaboration.Compared to small molecule and antibody-based drugs, siRNAs can act on virtually unrestricted choice of--otherwise "undruggable"--therapeutic targets, with high specificity and potency; while their easy manufacturing facilitates rapid lead optimization\[1\]. Therefore, siRNAs have the potential to effectively treat numerous diseases. Initial regulatory approvals of Alnylam's siRNA therapies for liver disorders in 2018-19 \[1-2\] validated clinical and commercial opportunity for such therapies. However, the major limiting factor for further success remains the lack of effective platforms 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 addressable disease indications.Mergo? addresses this challenge through its modular design based around a central RNA nanoscaffold. This can be functionalised with therapeutics and targeting molecules that recognise biomarkers on specific cells of interest only. This allows the platform to target only diseased cells, thus significantly reducing toxic side-effects from the therapy in other cells and tissues. Although previous Mergo? data demonstrated promising _in vitro_ and _in vivo_ results, highly competitive safety and favourable cost profiles, further validation of mechanism-of-action is required for specific tissue types.SUMMIT will develop an in-house siRNA targeted towards a specific extrahepatic tissue, and exploit the versatility of Mergo? using nucleic acid chemistry to improve delivery via tissue targeting. This will generate an in-house asset(s), speed candidate development, and act as a demonstrator for application of Mergo? to deliver diverse cargo (mRNAs, CRISPR therapeutics) and to target other indications. Consequently, Mergo? represents an attractive opportunity to capture a significant portion of the thriving gene therapy and delivery markets and could accelerate other Advanced Therapy Medicinal Products (ATMPs), through improved safety, efficacy and reduced cost of goods, especially compared to viral technologies.Pharmidex and MDC's unique expertise in advanced preclinical screening and imaging enables generation of preclinical data-pack for rapid commercialization and clinical advancement via licensing.Sixfold's broad IP portfolio and licensing strategy engages 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\.\[3\]Payne\_D\__Nature_\_574\_S1\_2019\.

Summit旨在开发和验证六倍的寡核苷酸输送系统Mergo？，用于递送（同时开发的）短距离RNA（SIRNA）基因沉默的货物（未公开）。 Summit将多学科合作伙伴与高度互补的专业知识和在交付成功项目方面的经验结合在一起，并在早期的研发协作中进行了快速的科学和商业进步。不可用的” - 具有高特异性和效力的治疗靶标；尽管它们易于制造促进了快速的铅优化\ [1 \]。因此，siRNA具有有效治疗多种疾病的潜力。 2018-19 \ [1-2 \]对ALNYLAM的SIRNA疗法的初步监管批准了此类疗法的临床和商业机会。但是，进一步成功的主要限制因素仍然是缺乏将siRNA的有效平台传递到特定患病细胞\ [4 \]的情况下。鉴于其细胞靶向特异性有限，货物载荷能力，高毒性和复杂/昂贵的制造限制了限制可寻址疾病的适应症，因此，当前的方法主要是GALNAC - 偶联，脂质纳米颗粒和病毒载体，是亚最佳的，是最佳的。通过基于中央RNA纳米尺度的模块化设计来应对这一挑战。这可以通过治疗剂和靶向分子来官能化，这些分子仅在特定的感兴趣细胞上识别生物标志物。这使平台仅靶向患病的细胞，从而显着减少其他细胞和组织中治疗的毒性副作用。虽然以前的mergo？数据显示出有希望的_和_in vivo_结果，高度竞争性的安全性和有利的成本概况，特定组织类型需要进一步验证行动机制。SUMMIT将发展针对特定肝外组织的内部sirna，并利用利用mergo的多功能性？使用核酸化学通过组织靶向改善递送。这将产生内部资产，速度候选人的发展，并充当Mergo应用的演示者？提供多种货物（mRNA，CRISPR疗法）并针对其他适应症。因此，Mergo？是一个有吸引力的机会，可以通过提高安全性，效力和商品成本降低，尤其是与病毒技术相比，可以通过提高安全性，功效和降低商品来捕捉大部分蓬勃发展的基因疗法和递送市场，并可以加速其他先进的药物药物（ATMP）。先进的临床前筛选和成像方面的专业知识能够通过许可生成快速商业化和临床进步的临床前数据包。Sixfold的广泛的IP组合和许可策略使整个生物制药供应链都吸引了整个Biopharmaceutical供应链，从而为更广泛的英国生活科学领域提供了多样的好处。 1 \] lam \ _j.k.w \ _et \ _Al。 \ [2 \] alnylam \ _press \ _release \ _10 \ _August \ _2018 \。\ [3 \]