Mechanisms of alginate/rAAV gene vector encapsulation and release for enhanced, safe rAAV-mediated therapeutic gene transfer in human meniscal lesions

• Applicant: Jagadeesh Venkatesan, Ph.D.
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2021 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 461955244

• Final Report Year: 2023

Final Report Abstract

The currently funded project allowed to generate highly promising data showing the value of alginate (AlgPH155) hydrogels as effective and safe systems to deliver clinically adapted therapeutic rAAV (FGF-2, TGF-β) vectors capable of stimulating the reparative activities in human meniscal fibrochondrocytes in vitro and in human experimental meniscal lesions in situ (relative to control conditions). Work continues to finalize the objectives 1 and 2 (tests of the approach in the presence of the neutralizing anti-AAV capsid antibody A20) and to perform objective 3 (experiments in vivo) that were delayed because of the COVID-19 pandemic limiting the access to the laboratory and facilities. Dissemination of the generated data at national and international conferences highlights the significance and potential impact of the research in the scientific community.

Publications

• Benefits of alginate hydrogel-guided delivery of an rAAV FGF-2 vector to activate the reparative properties of human meniscal fibrochondrocytes. 2022 OARSI World Congress on Osteoarthritis, 2022, Berlin, Germany
  Venkatesan J. K. et al.
  
• Overexpression of TGF- via rAAV gene transfer in an alginate hydrogel activates the healing capacities of human meniscal fibrochondrocytes. 2022 OARSI World Congress on Osteoarthritis, 2022, Berlin, Germany
  Venkatesan J. K. et al.
  
• rAAV-mediated FGF-2 overexpression via alginate hydrogel delivery stimulates the reparative abilities of human meniscal fibrochondrocytes. 68th Annual Meeting of the Orthopaedic Research Society (ORS), 2022, Tampa, Florida, USA
  Venkatesan J. K. et al.
  
• Alginate hydrogel-guided rAAV-mediated FGF-2 and TGF- overexpression activates the reparative properties in human meniscal lesion. 69th Annual Meeting of the Orthopaedic Research Society (ORS), 2023, Dallas, Texas, USA
  Venkatesan J. K. et al.
  
• Benefits of alginate hydrogel-guided rAAV-mediated FGF-2 and TGF- overexpression on the reparative properties of human meniscal lesions. 2023 Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU), 2023, Berlin, Germany
  Venkatesan J. K. et al.
  
• rAAV-mediated FGF-2 and TGF- overexpression via alginate hydrogel delivery stimulates the reparative abilities of human meniscal lesions in situ. 2023 OARSI World Congress on Osteoarthritis, 2023, Denver, Colorado, USA
  Venkatesan J. K. et al.