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.

这个小企业创新研究（SBIR）二期项目的更广泛的影响/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的市场正在迅速增长，基因治疗的市场也在迅速增长，这就需要一种通用的口服药物递送平台。该平台将通过减少重复注射的需求对社会产生积极影响。该系统将通过改善口服利用度和向肠细胞的运输以及随后蛋白质向血流中的分泌来改善注射剂的施用的容易性。这也将允许用于肠道疾病的治疗剂的局部递送，这些肠道疾病目前受到粘液渗透不良的阻碍，并且代表数十亿美元的市场。这项技术的成功转化将使制药公司、患者和支付者受益，为广泛的治疗提供口服给药平台。这项小型企业创新研究（SBIR）II期项目解决了口服脂质纳米颗粒给药后改善胃肠道蛋白质系统表达的问题。消化道的作用是分解脂质和核酸，因此基因递送载体的存活和将货物递送到肠道是非常具有挑战性的。该项目提出了一种新的脂质纳米颗粒系统，能够保护遗传货物在肠细胞中产生蛋白质表达，然后分泌到血液中进行体循环。这个过程将以前注射的蛋白质药物转化为易于口服的药物。研究目的是筛选和优化几种脂质组分以及核酸，以改善口服给药后蛋白质分泌到血液中的表达。本研究将在体内筛选多种制剂和货物，并测量口服脂质纳米粒后的血清蛋白水平。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，进一步增加口服脂质纳米粒的潜在治疗靶点范围。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。