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Updated: Jun 2, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Myeloma xenograft destruction by a nonviral vector delivering oncolytic infectious nucleic acid
Elizabeth M Hadac1, Elizabeth J Kelly, Stephen J Russell
1Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
Abstract:
The feasibility of using a nonviral vector formulation to initiate an oncolytic viral infection has not been previously demonstrated. We therefore sought to determine whether infectious nucleic acid (INA) could be used in place of virus particles to initiate an oncolytic picornavirus infection in vivo. Infectious RNA encoding coxsackievirus A21 (CVA21) was transcribed from plasmid DNA using T7 polymerase. Within 48 hours of injecting this RNA into KAS6/1 myeloma xenografts, high titers of infectious CVA21 virions were detected in the bloodstream. Tumors regressed rapidly thereafter and mice developed signs of myositis. At euthanasia, CVA21 was recovered from regressing tumors and from skeletal muscles. Treatment outcomes were comparable following intratumoral injection of naked RNA or fully infectious CVA21 virus. Dose-response studies showed that an effective oncolytic infection could be established by intratumoral injection of 1 µg of infectious RNA. The oncolytic infection could also be initiated by intravenous injection of infectious RNA. Our study demonstrates that INA is a highly promising alternative drug formulation for oncolytic virotherapy.
Insights
Infectious nucleic acid (INA) effectively initiated oncolytic picornavirus infections in vivo, offering a promising nonviral alternative for oncolytic virotherapy. This approach demonstrated comparable outcomes to traditional virus particles.
Area of Science:
- Oncolytic virotherapy
- Molecular virology
- Cancer therapeutics
Background:
- Nonviral vector formulations for initiating oncolytic viral infections remain largely unexplored.
- Developing alternative delivery methods for oncolytic viruses is crucial for advancing cancer treatment.
Purpose of the Study:
- To investigate the feasibility of using infectious nucleic acid (INA) as a nonviral alternative to virus particles for initiating oncolytic picornavirus infections in vivo.
- To compare the efficacy of INA-initiated infections with traditional CVA21 virus treatments.
Main Methods:
- Infectious RNA encoding coxsackievirus A21 (CVA21) was transcribed from plasmid DNA.
- RNA was administered intratumorally or intravenously into KAS6/1 myeloma xenografts in mice.
- Viral titers, tumor regression, and viral recovery from tissues were assessed.
Main Results:
- Intratumoral injection of CVA21 INA led to high titers of infectious CVA21 virions in the bloodstream within 48 hours.
- Rapid tumor regression and signs of myositis were observed in treated mice.
- Comparable treatment outcomes were achieved using either naked RNA or infectious CVA21 virus, with effective infection initiated by as little as 1 µg of RNA.
Conclusions:
- Infectious nucleic acid (INA) can effectively initiate oncolytic picornavirus infections in vivo, demonstrating its potential as a nonviral drug formulation.
- This INA-based approach offers a promising and effective alternative for oncolytic virotherapy, comparable to conventional viral treatments.
