SBIR Phase II: Development Of An Orally Administered Gene Therapy For Granulocyte Colony-Stimulating Factor

SBIR II 期：开发粒细胞集落刺激因子口服基因疗法

• 批准号: 2133290
• 负责人: Timothy Day
• 金额: $ 96.73万
• 依托单位: DNALITE THERAPEUTICS, INC.
• 依托单位国家: 美国
• 项目类别: Cooperative Agreement
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2133290&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Development; Orally

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is an oral delivery platform that can deliver various drugs to the gastrointestinal tract. The market for novel biologics and oral formulations of currently injectable biologics is increasing rapidly, as is the market for gene therapies, necessitating a versatile oral drug delivery platform. This platform would positively impact society by reducing the need for repeated injections. This system would improve ease of administration of injectables by improving oral availability and the transport to the intestinal cells, and subsequent secretion of the protein into the bloodstream. This would also allow for local delivery of therapeutics for intestinal diseases which currently are hampered by poor mucus penetration and represent a multibillion-dollar market. Successful translation of this technology would benefit pharmaceutical companies, patients, and payers by providing an oral delivery platform for a broad range of therapeutics.This Small Business Innovation Research (SBIR) Phase II project addresses the problem of improving systemic expression of a protein from the gastrointestinal tract following oral lipid nanoparticle delivery. The role of digestive tract is to breakdown lipids and nucleic acids and it has therefore been very challenging to for gene delivery vehicles to survive and deliver cargo to the intestine. The project advances a new lipid nanoparticle system able to protect the genetic cargo to generate protein expression in intestinal cells later secreted into the bloodstream for systemic circulation. This process converts previously injected protein drugs into an easily administered oral drug. The research objectives are to screen and optimize several of the lipid components as well as the nucleic acid to improve secreted expression of a protein into the blood after oral delivery. This research will screen multiple formulations and cargos in vivo and measure serum protein levels after oral lipid nanoparticle delivery. The anticipated technical results are that the level of secreted protein will improve 10x from the initial formulation, further increasing the scope of potential therapeutic targets for the oral lipid nanoparticle.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该小企业创新研究 (SBIR) 第二阶段项目更广泛的影响/商业潜力是一个口服给药平台，可以将各种药物输送到胃肠道。新型生物制剂和目前可注射生物制剂的口服制剂市场正在迅速增长，基因疗法市场也在迅速增长，因此需要一个多功能的口服药物输送平台。该平台将通过减少重复注射的需要对社会产生积极影响。该系统将通过提高口服利用率和向肠细胞的运输以及随后将蛋白质分泌到血液中来提高注射剂的给药便利性。这也将允许对肠道疾病进行局部治疗，这些疾病目前因粘液渗透性差而受到阻碍，并且代表了一个数十亿美元的市场。这项技术的成功转化将为广泛的治疗提供口服给药平台，从而使制药公司、患者和付款人受益。这个小型企业创新研究 (SBIR) II 期项目解决了改善蛋白质系统表达的问题口服脂质纳米颗粒递送后的胃肠道。消化道的作用是分解脂质和核酸，因此基因递送载体的生存和将货物递送到肠道非常具有挑战性。该项目提出了一种新的脂质纳米颗粒系统，能够保护遗传物质，在肠道细胞中产生蛋白质表达，随后分泌到血液中进行全身循环。该过程将先前注射的蛋白质药物转化为易于给药的口服药物。研究目标是筛选和优化几种脂质成分以及核酸，以改善口服给药后蛋白质分泌到血液中的表达。这项研究将在体内筛选多种制剂和货物，并测量口服脂质纳米颗粒递送后的血清蛋白水平。预期的技术结果是，分泌蛋白的水平将比初始配方提高10倍，进一步扩大了口服脂质纳米颗粒的潜在治疗靶点范围。该奖项反映了NSF的法定使命，并通过使用评估结果被认为值得支持。基金会的智力价值和更广泛的影响审查标准。