Department of Bioscience and Bioengineering, Indian Institute of Technology Bombay, Mumbai, 400076, India.
Tata Memorial Centre Advanced Centre for Treatment, Research and Education in Cancer, Navi Mumbai, 410210, India.
Biomed Phys Eng Express. 2024 Jun 5;10(4). doi: 10.1088/2057-1976/ad4e3a.
Lentiviral transduction is widely used in research, has shown promise in clinical trials involving gene therapy and has been approved for CAR-T cell immunotherapy. However, most modifications are doneand rely on systemic administration of large numbers of transduced cells for clinical applications. A novel approach utilizingbiomaterial-based gene delivery can reduce off-target side effects while enhancing effectiveness of the manipulation process. In this study, poly(ethylene glycol) diacrylate (PEGDA)-based scaffolds were developed to enablelentivirus-mediated transduction. Compared to other widely popular biomaterials, PEGDA stands out due to its robustness and cost-effectiveness. These scaffolds, prepared via cryogelation, are capable of flowing through surgical needles in bothandconditions, and promptly regain their original shape. Modification with poly(L-lysine) (PLL) enables lentivirus immobilization while interconnected macroporous structure allows cell infiltration into these matrices, thereby facilitating cell-virus interaction over a large surface area for efficient transduction. Notably, these preformed injectable scaffolds demonstrate hemocompatibility, cell viability and minimally inflammatory response as shown by ourandstudies involving histology and immunophenotyping of infiltrating cells. This study marks the first instance of using preformed injectable scaffolds for delivery of lentivectors, which offers a non-invasive and localized approach for delivery of factors enablinglentiviral transduction suitable for both tissue engineering and immunotherapeutic applications.
慢病毒转导被广泛应用于研究领域，在基因治疗的临床试验中显示出前景，并已被批准用于 CAR-T 细胞免疫疗法。然而，大多数修饰都是在and条件下通过全身给予大量转导细胞来实现的，这在临床应用中具有局限性。一种新的利用生物材料的基因传递方法可以减少脱靶副作用，同时增强操作过程的有效性。在这项研究中，开发了基于聚乙二醇二丙烯酸酯（PEGDA）的支架来实现慢病毒介导的转导。与其他广泛使用的生物材料相比，PEGDA 因其坚固性和成本效益而脱颖而出。这些通过冷冻凝胶化制备的支架可以在and条件下通过手术针流动，并迅速恢复其原始形状。通过聚 L-赖氨酸（PLL）的修饰可以实现慢病毒的固定化，而互穿的大孔结构允许细胞渗透到这些基质中，从而促进细胞与病毒在大表面积上的相互作用，实现高效转导。值得注意的是，这些预制的可注射支架表现出良好的血液相容性、细胞活力和最小的炎症反应，这一点通过我们的and研究得到了证实，该研究涉及到渗透细胞的组织学和免疫表型分析。这项研究首次使用预制的可注射支架来递送慢病毒载体，为递送因子提供了一种非侵入性和局部性的方法，适用于组织工程和免疫治疗应用。
