Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.
Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA; Weldon School of Biomedical Engineering, Purdue University, 206 S Martin Jischke Dr., West Lafayette, IN 47907, USA.
J Control Release. 2022 May;345:586-600. doi: 10.1016/j.jconrel.2022.03.045. Epub 2022 Mar 26.
A group of nucleic acids and oligonucleotides play various roles in the innate immune system. They can stimulate pattern recognition receptors to activate innate immune cells, encode immunostimulatory proteins or peptides, or silence specific genes to block negative regulators of immune cells. Given the limitations of current cancer immunotherapy, there has been increasing interest in harnessing innate immune responses by nucleic acids and oligonucleotides. The poor biopharmaceutical properties of nucleic acids and oligonucleotides make it critical to use carriers that can protect them in circulation, retain them in the tumor microenvironment, and bring them to intracellular targets. Therefore, various gene carriers have been repurposed to deliver nucleic acids and oligonucleotides for cancer immunotherapy and improve their safety and activity. Here, we review recent studies that employed carriers to enhance the functions of nucleic acids and oligonucleotides and overall immune responses to cancer, and discuss remaining challenges and future opportunities in the development of nucleic acid-based immunotherapeutics.
一组核酸和寡核苷酸在先天免疫系统中发挥着各种作用。它们可以刺激模式识别受体激活先天免疫细胞，编码免疫刺激性蛋白或肽，或沉默特定基因以阻断免疫细胞的负调节剂。鉴于当前癌症免疫疗法的局限性，人们越来越感兴趣地利用核酸和寡核苷酸来引发先天免疫反应。核酸和寡核苷酸的生物制药性质较差，因此必须使用载体来保护它们在循环中的稳定性，保留它们在肿瘤微环境中的稳定性，并将它们带到细胞内靶标。因此，各种基因载体已被重新用于传递核酸和寡核苷酸以进行癌症免疫治疗，并提高它们的安全性和活性。在这里，我们综述了最近利用载体来增强核酸和寡核苷酸的功能以及整体免疫反应以对抗癌症的研究，并讨论了核酸免疫疗法发展中仍然存在的挑战和未来机遇。
