Injectable Hydrogel Depots for Self-replicating mRNA Vaccine Delivery

而金黄色葡萄球菌(SA)通常无症状地定植于健康人的皮肤和鼻子 人类，严重的疾病可以由血液、骨骼、皮肤和肺部的感染以及 导管和假体装置。使用目前批准的治疗方法，约三分之一的患者被诊断为 沙门氏菌血症会导致死亡，每年死亡人数超过艾滋病毒、结核病和病毒性肝炎。 加在一起。R01将开发一种可注射疫苗仓库，包括：(A)以前发表的阳离子 用于凝聚和电荷中和阴离子自复制信使核糖核酸(SR-mRNA)疫苗的聚合物 纳米粒子(即“聚合物”)，然后被结合到(B)我们最近报道的 可注射生物降解凝胶N-琥珀酰壳聚糖(S-CS)和氧化海藻酸盐(O-ALG)。归根结底， 临时CS-ALG仓库完全生物降解为无毒副产品，并被淘汰。这个项目 将产生一种自我免疫的生物材料技术，一旦应用，就会在免疫方面具有优势 而不是反复全身注射。

While Staphylococcus aureus (SA) commonly asymptomatically colonizes the skin and nose of healthy humans, severe disease can result from infection of the blood, bone, skin, and lungs, as well as sites of catheters and prosthetic devices. With currently approved therapy, about one-third of patients diagnosed with SA bacteremia succumb, accounting for more annual deaths than HIV, tuberculosis, and viral hepatitis combined. This R01 will develop an injectable vaccine depot comprising: (a) previously published cationic polymers to condense and charge neutralize anionic self-replicating mRNA (SR-mRNA) vaccines into nanometer-sized particles (i.e., “polyplexes”) that are then incorporated within (b) our recently reported injectable biodegradable gel of N-succinyl-chitosan (S-CS) and oxidized alginate (O-Alg). Ultimately, the temporary CS-Alg depots completely biodegrade into non-toxic by-products that are eliminated. This project will generate a self-immunizing biomaterials technology that is applied ONCE that is superior in immunization versus repeated systemic bolus injections.