Abstract：
DNA vaccines represent an innovative approach for the immunization of diverse diseases. However, their clinical trial outcomes are constrained by suboptimal transfection efficiency and immunogenicity. In this work, we present a universal methodology involving the codelivery of Toll-like receptor 7/8 agonists (TLR7/8a) and antigen gene using TLR7/8a-conjugated peptide-coated poly(β-amino ester) (PBAE) nanoparticles (NPs) to augment delivery efficiency and immune response. Peptide-TLR7/8a-coated PBAE NPs exhibit advantageous biophysical attributes, encompassing diminutive particle dimensions, nearly neutral ζ potential, and stability in the physiological environment. This synergistic approach not only ameliorates the stability of plasmid DNA (pDNA) and gene delivery efficacy but also facilitates subsequent antigen production. Furthermore, under optimal formulation conditions, the TLR7/8a-conjugated peptide coated PBAE NPs exhibit a potent capacity to induce robust immune responses. Collectively, this nanoparticulate gene delivery system demonstrates heightened transfection efficacy, stability, biodegradability, immunostimulatory effect, and low toxicity, making it a promising platform for the clinical advancement of DNA vaccines.
摘要：
DNA疫苗代表了免疫多种疾病的创新方法。然而,他们的临床试验结果受到次优转染效率和免疫原性的限制.在这项工作中,我们提出了一种通用的方法,涉及使用TLR7/8a缀合的肽包被的聚(β-氨基酯)(PBAE)纳米颗粒(NP)共同递送Toll样受体7/8激动剂(TLR7/8a)和抗原基因,以提高递送效率和免疫应答.肽-TLR7/8a包被的PBAENP表现出有利的生物物理属性，包括微小的颗粒尺寸，接近中性ζ电位，在生理环境中的稳定性。这种协同方法不仅改善了质粒DNA(pDNA)的稳定性和基因递送功效,而且促进了随后的抗原产生。此外，在最佳配方条件下，TLR7/8a缀合的肽包被的PBAENP表现出诱导强免疫应答的有效能力。总的来说，这种纳米颗粒基因递送系统显示出增强的转染效力，稳定性,生物降解性，免疫刺激作用，低毒性,使其成为DNA疫苗临床发展的有前途的平台。
