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

这个小企业创新研究(SBIR)第二阶段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。目前可注射生物制品的新型生物制品和口服制剂的市场正在迅速增长，基因疗法的市场也是如此，这就需要一个多功能的口服药物输送平台。这一平台将减少重复注射的需要，从而对社会产生积极影响。这一系统将通过改善口服利用度和向肠道细胞的传输，以及随后蛋白质分泌到血液中，来改善注射的易用性。这也将使当地能够提供肠道疾病的治疗药物，这些疾病目前受到粘液渗透不良的阻碍，代表着一个数十亿美元的市场。这项技术的成功转化将为制药公司、患者和支付者提供一个广泛的治疗口腔递送平台。这个小企业创新研究(SBIR)第二阶段项目致力于改善口服脂质纳米粒递送后胃肠道蛋白质的系统表达。消化道的作用是分解脂质和核酸，因此，基因递送载体要存活并将货物运送到肠道一直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，在肠道细胞中产生蛋白质表达，然后分泌到血液中进行全身循环。这一过程将以前注射的蛋白质药物转化为易于服用的口服药物。研究目标是筛选和优化几种脂类成分以及核酸，以提高蛋白质在口服后进入血液的分泌表达。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粒给药后的血清蛋白水平。预期的技术成果是分泌蛋白水平将比最初的配方提高10倍，进一步扩大口服脂质纳米颗粒潜在治疗目标的范围。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.