Biosilicified oncolytic adenovirus for cancer viral gene therapy

Area of Science:

• Biotechnology
• Nanomedicine
• Cancer Gene Therapy

Background:

• Oncolytic adenoviruses (OAs) show promise for cancer gene therapy but face challenges like liver sequestration and neutralizing antibodies (nAbs).
• These factors limit OA accumulation in tumors, reducing their therapeutic efficacy.
• Developing strategies to overcome these barriers is crucial for advancing OA-based treatments.

Purpose of the Study:

• To enhance the tumor-targeting ability and therapeutic efficacy of OAs using a biosilicification method.
• To investigate the impact of silica encapsulation on OA biodistribution, immune evasion, and antitumor activity.
• To evaluate the biocompatibility of the biosilicified OA formulation.

Main Methods:

• Encapsulation of an OA encoding the anticancer gene Trail (OA-Trail) with silica using a biosilicification technique, creating OA-Trail@SiO₂.
• In vitro and in vivo studies to assess viral clearance, nAb degradation, biodistribution, and tumor inhibition.
• Biocompatibility assessments of the biosilicified OA formulation.

Main Results:

• Biosilicified OA-Trail (OA-Trail@SiO₂) demonstrated significantly reduced viral clearance in the liver compared to native OAs.
• The silica encapsulation effectively evaded degradation by preexisting neutralizing antibodies (nAbs).
• OA-Trail@SiO₂ exhibited enhanced tumor accumulation and potent tumor inhibition, with demonstrated biocompatibility.

Conclusions:

• Biosilicification offers a viable strategy to overcome key limitations of OAs in cancer gene therapy.
• Silica encapsulation improves OA delivery to tumors by enhancing circulation time and evading immune responses.
• This approach presents a promising alternative for developing more effective oncolytic adenovirus-based cancer therapies.