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Scaffold Based Gene Delivery for Immunotherapeutic Applications
CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2022; 43(S 01): S1-S19
DOI: DOI: 10.1055/s-0042-1755513
Correspondence to: prakriti@iitb.ac.in
Background: Gene delivery is one of the major achievements in the field of immunotherapy, but the cost and complexity of manufacturing large numbers of genetically programmed cells remain a major hurdle. We thereby illustrate a method to deliver genes to cells in native microenvironment thus overcoming existing limitations.
Materials and Methods: Polyethylene glycol–based scaffold implant was fabricated and carbamide chemistry was used to conjugate poly-L-lysine and immobilize gene carrying lentiviruses on the scaffold. This implant was characterized for physical and biological properties. Further, GFP and luciferase expressing lentiviruses were loaded in the scaffold and efficiency of gene delivery was characterized.
Results: Characterization of scaffold showed a highly interconnected macroporous structure in SEM, thereby revealing a higher surface area for immobilization of lentiviruses. The scaffold was also biocompatible and hemocompatible. Further, conjugation of poly-L-lysine significantly improved the immobilization of lentiviruses on the scaffold. In vitro studies show efficient delivery of GFP gene into HEK293T cells via the scaffold loaded with GFP expressing lentiviruses. Mice implanted with luciferase expressing lentivirus loaded scaffold showed higher transduction efficiency when compared to bolus lentivirus delivery.
Conclusion: Here, we demonstrate a practical, low-cost, broadly applicable gene delivery strategy that can genetically program cells without the requirement for ex vivo manipulation of patient cells. Further, engineering techniques can be used to attract and modify specific cells for various disease settings.
Publication History
Article published online:
22 August 2022
© 2022. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
Correspondence to: prakriti@iitb.ac.in
Background: Gene delivery is one of the major achievements in the field of immunotherapy, but the cost and complexity of manufacturing large numbers of genetically programmed cells remain a major hurdle. We thereby illustrate a method to deliver genes to cells in native microenvironment thus overcoming existing limitations.
Materials and Methods: Polyethylene glycol–based scaffold implant was fabricated and carbamide chemistry was used to conjugate poly-L-lysine and immobilize gene carrying lentiviruses on the scaffold. This implant was characterized for physical and biological properties. Further, GFP and luciferase expressing lentiviruses were loaded in the scaffold and efficiency of gene delivery was characterized.
Results: Characterization of scaffold showed a highly interconnected macroporous structure in SEM, thereby revealing a higher surface area for immobilization of lentiviruses. The scaffold was also biocompatible and hemocompatible. Further, conjugation of poly-L-lysine significantly improved the immobilization of lentiviruses on the scaffold. In vitro studies show efficient delivery of GFP gene into HEK293T cells via the scaffold loaded with GFP expressing lentiviruses. Mice implanted with luciferase expressing lentivirus loaded scaffold showed higher transduction efficiency when compared to bolus lentivirus delivery.
Conclusion: Here, we demonstrate a practical, low-cost, broadly applicable gene delivery strategy that can genetically program cells without the requirement for ex vivo manipulation of patient cells. Further, engineering techniques can be used to attract and modify specific cells for various disease settings.
No conflict of interest has been declared by the author(s).
Publication History
Article published online:
22 August 2022
© 2022. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India