Neha Dalal, Hiren Dandia, Arvind Ingle, Prakriti Tayalia
{"title":"Surface-modified injectable poly(ethylene-glycol) diacrylate-based cryogels for localized gene delivery.","authors":"Neha Dalal, Hiren Dandia, Arvind Ingle, Prakriti Tayalia","doi":"10.1088/2057-1976/ad4e3a","DOIUrl":null,"url":null,"abstract":"<p><p>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 done<i>ex vivo</i>and rely on systemic administration of large numbers of transduced cells for clinical applications. A novel approach utilizing<i>in situ</i>biomaterial-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 enable<i>in situ</i>lentivirus-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 both<i>in vitro</i>and<i>in vivo</i>conditions, 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 our<i>in vitro</i>and<i>in vivo</i>studies 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 enabling<i>in situ</i>lentiviral transduction suitable for both tissue engineering and immunotherapeutic applications.</p>","PeriodicalId":8896,"journal":{"name":"Biomedical Physics & Engineering Express","volume":null,"pages":null},"PeriodicalIF":1.3000,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedical Physics & Engineering Express","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1088/2057-1976/ad4e3a","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
引用次数: 0
Abstract
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 doneex vivoand rely on systemic administration of large numbers of transduced cells for clinical applications. A novel approach utilizingin situbiomaterial-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 enablein situlentivirus-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 bothin vitroandin vivoconditions, 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 ourin vitroandin vivostudies 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 enablingin situlentiviral transduction suitable for both tissue engineering and immunotherapeutic applications.
期刊介绍:
BPEX is an inclusive, international, multidisciplinary journal devoted to publishing new research on any application of physics and/or engineering in medicine and/or biology. Characterized by a broad geographical coverage and a fast-track peer-review process, relevant topics include all aspects of biophysics, medical physics and biomedical engineering. Papers that are almost entirely clinical or biological in their focus are not suitable. The journal has an emphasis on publishing interdisciplinary work and bringing research fields together, encompassing experimental, theoretical and computational work.