Kirti Sneha, Patel Komal, Das Subhadeep, Shrimali Paresh, Samanta Sonali, Kumar Rakesh, Chatterjee Debdeep, Ghosh Dhiman, Kumar Ashutosh, Tayalia Prakriti, Maji Samir K
ACS Biomater Sci Eng. 2019 Jan 14;5(1):126-138. doi: 10.1021/acsbiomaterials.8b00248. Epub 2018 Jul 27.
Amyloid fibrils are cross-β-sheet-rich protein/peptide fibrils that are typically associated with neurodegenerative diseases such as Parkinson's and Alzheimer's disease. Recently, functional amyloids have been discovered where amyloids are implicated in performing normal physiological functions of the host organism rather than creating diseases. The ability of amyloids to interact with the cell membrane and other small biomolecules exhibits its great potential to be used as a biomaterial for cell adhesion and gene delivery system. Given the established ability of semen-derived amyloids to concentrate HIV in semen and that of charged polymers as an enhancer of retroviral gene transfer, we hypothesized that charged amyloid fibrils can augment virus-mediated delivery system. We show that amyloids of α-synuclein formed in the presence and absence of cationic polymers chitosan and amyloid of poly-l-lysine can interact with lentiviral particles and enhance transduction efficiency in cells. The amyloid nanofibrils increase transduction efficiency up to ∼4 fold similar to widely used cationic polymer Polybrene. This study shows that amyloid nanofibril scaffolds may be used as targeted gene delivery systems.
淀粉样纤维是富含交叉β-折叠的蛋白质/肽纤维，通常与神经退行性疾病如帕金森病和阿尔茨海默病相关。最近，发现了功能性淀粉样蛋白，其中淀粉样蛋白参与宿主生物体的正常生理功能而非引发疾病。淀粉样蛋白与细胞膜和其他小生物分子相互作用的能力显示出其作为细胞黏附生物材料和基因递送系统的巨大潜力。鉴于精液衍生的淀粉样蛋白在精液中浓缩HIV的既定能力以及带电聚合物作为逆转录病毒基因转移增强剂的能力，我们推测带电淀粉样纤维可以增强病毒介导的递送系统。我们表明，在存在和不存在阳离子聚合物壳聚糖的情况下形成的α-突触核蛋白淀粉样蛋白以及聚-L-赖氨酸淀粉样蛋白可以与慢病毒颗粒相互作用并提高细胞中的转导效率。淀粉样纳米纤维将转导效率提高至约4倍，类似于广泛使用的阳离子聚合物聚凝胺。这项研究表明，淀粉样纳米纤维支架可作为靶向基因递送系统。
