Northwestern University, Department of Chemical & Biological Engineering, 2145 Sheridan Rd, Tech Building E-136, Evanston, IL 60208, USA.
Expert Opin Drug Deliv. 2013 Apr;10(4):499-509. doi: 10.1517/17425247.2013.764864. Epub 2013 Jan 25.
Gene delivery from hydrogel biomaterials provides a fundamental tool for a variety of clinical applications including regenerative medicine, gene therapy for inherited disorders and drug delivery. The high water content and mild gelation conditions of hydrogels support their use for gene delivery by preserving activity of lentiviral vectors and acting to shield vectors from any host immune response.
Strategies to control lentiviral entrapment within and retention/release from hydrogels are reviewed. The authors discuss the ability of hydrogel design parameters to control the transgene expression profile and the capacity of hydrogels to protect vectors from (and even modulate) the host immune response.
Delivery of genetic vectors from scaffolds provides a unique opportunity to capitalize on the potential synergy between the biomaterial design for cell processes and gene delivery. Hydrogel properties can be tuned to directly control the events that determine the tissue response to controlled gene delivery, which include the extent of cell infiltration, preservation of vector activity and vector retention. While some design parameters have been identified, numerous opportunities for investigation are available in order to develop a complete model relating the biomaterial properties and host response to gene delivery.
水凝胶生物材料的基因传递为各种临床应用提供了一个基本工具,包括再生医学、遗传性疾病的基因治疗和药物输送。水凝胶的高含水量和温和的凝胶条件支持它们用于基因传递,因为它们可以保持慢病毒载体的活性,并防止载体受到任何宿主免疫反应的影响。
本文综述了控制慢病毒在水凝胶内的包埋和保留/释放的策略。作者讨论了水凝胶设计参数控制转基因表达谱的能力,以及水凝胶保护载体免受(甚至调节)宿主免疫反应的能力。
从支架输送遗传载体为利用细胞过程和基因传递之间的潜在协同作用提供了一个独特的机会。可以调整水凝胶的特性来直接控制决定组织对受控基因传递反应的事件,包括细胞浸润的程度、载体活性的保持和载体的保留。虽然已经确定了一些设计参数,但为了开发一个完整的模型,将生物材料特性和宿主对基因传递的反应联系起来,还有许多研究机会。