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Updated: Jul 4, 2026
High-Efficiency Transduction of Liver Cancer Cells by Recombinant Adeno-Associated Virus Serotype 3 Vectors
Published on: March 22, 2011
Development of recombinant adeno-associated virus and adenovirus cocktail system for efficient hTERTC27
1Department of Chemistry, Institute of Molecular Biology, The University of Hong Kong, Pokfulam, Hong Kong, China.
Abstract:
The low in vivo transduction efficiency of recombinant adeno-associated virus (rAAV) and the undesirably strong immunogenicity of adenovirus (rAdv) have limited their clinical utilization in cancer gene therapy. We have previously demonstrated that intratumoral injection of rAAV expressing a C-terminal polypeptide of human telomerase reverse transcriptase (rAAV-hTERTC27) effectively inhibits the growth of glioblastoma xenografts in nude mice. To further improve its efficacy, we combined rAAV-hTERTC27 with rAdv and investigated the efficiency of the cocktail vectors in vivo. At a nontherapeutic dose (1 x 10(8) plaque-forming units (PFUs)), rAdv-null and rAdv-hTERTC27 were equipotent in enhancing the therapeutic efficacy of rAAV-hTERTC27 (1.5 x 10(11) v.g.), and complete tumor regression was achieved in 25% of the treated animals. Importantly, the combination of rAAV-hTERTC27 and a therapeutic dose (2.5 x 10(9) PFU) of rAdv-hTERTC27 significantly augmented the therapeutic effects and led to a 38% complete tumor regression rate. In vivo optical imaging also showed that rAAV-luc/rAdv-luc cocktail vectors could synergistically enhance the early transient and latent sustained expression of luciferase, as compared to rAdv-luc and rAAV-luc alone. These findings suggest that the combination of rAAV-hTERTC27 and a therapeutic dose of rAdv-hTERTC27 is potentially a promising treatment for glioblastoma, and the rAAV/rAdv cocktail vector system warrants further development for cancer gene therapy.
Insights
Combining recombinant adeno-associated virus (rAAV) with adenovirus (rAdv) enhances glioblastoma gene therapy. This rAAV/rAdv cocktail shows promising results, achieving significant tumor regression in preclinical models.
Area of Science:
- Oncology
- Gene Therapy
- Viral Vectors
Background:
- Recombinant adeno-associated virus (rAAV) and adenovirus (rAdv) have limitations in cancer gene therapy due to low transduction efficiency and immunogenicity, respectively.
- Previous studies showed rAAV expressing human telomerase reverse transcriptase (rAAV-hTERTC27) inhibits glioblastoma growth.
Purpose of the Study:
- To improve the efficacy of rAAV-hTERTC27 for glioblastoma treatment by combining it with rAdv.
- To investigate the in vivo efficiency of a combined rAAV/rAdv cocktail vector system.
Main Methods:
- Combination therapy using rAAV-hTERTC27 with different doses of rAdv (null or expressing hTERTC27).
- Assessment of tumor growth inhibition and complete tumor regression rates in glioblastoma xenografts.
- In vivo optical imaging to evaluate synergistic gene expression using luciferase reporter vectors (rAAV-luc/rAdv-luc).
Main Results:
- A non-therapeutic dose of rAdv enhanced rAAV-hTERTC27 efficacy, leading to 25% complete tumor regression.
- A therapeutic dose of rAdv-hTERTC27 combined with rAAV-hTERTC27 significantly improved outcomes, achieving a 38% complete tumor regression rate.
- Cocktail vectors demonstrated synergistic enhancement of both early transient and sustained gene expression compared to individual vectors.
Conclusions:
- The combination of rAAV-hTERTC27 and a therapeutic dose of rAdv-hTERTC27 is a promising strategy for glioblastoma gene therapy.
- The rAAV/rAdv cocktail vector system shows potential for further development in cancer gene therapy applications.
