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Poxviruses as Gene Therapy Vectors: Generating Poxviral Vectors Expressing Therapeutic Transgenes
Steven J Conrad1, Jia Liu2,3
1Department of Microbiology and Immunology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA.
Abstract:
Treatments with poxvirus vectors can have long-lasting immunological impact in the host, and thus they have been extensively studied to treat diseases and for vaccine development. More importantly, the oncolytic properties of poxviruses have led to their development as cancer therapeutics. Two poxviruses, vaccinia virus (VACV) and myxoma virus (MYXV), have been extensively studied as virotherapeutics with promising results. Vaccinia virus vectors have advanced to the clinic and have been tested as oncolytic therapeutics for several cancer types with successes in phase I/II clinical trials. In addition to oncolytic applications, MYXV has been explored for additional applications including immunotherapeutics, purging of cancer progenitor cells, and treatments for graft-versus-host diseases. These novel therapeutic applications have encouraged its advancement into clinical trials. To meet the demands of different treatment needs, VACV and MYXV can be genetically engineered to express therapeutic transgenes. The engineering process used in poxvirus vectors can be very different from that of other DNA virus vectors (e.g., the herpesviruses). This chapter is intended to serve as a guide to those wishing to engineer poxvirus vectors for therapeutic transgene expression and to produce viral preparations for preclinical studies.
Insights
Poxvirus vectors, including vaccinia virus (VACV) and myxoma virus (MYXV), show promise as oncolytic cancer therapeutics and for other medical treatments. This guide details engineering these poxvirus vectors for therapeutic transgene expression and preclinical studies.
Area of Science:
- Virology
- Immunology
- Oncology
Background:
- Poxvirus vectors are studied for their long-lasting immunological effects, vaccine development, and especially for cancer treatment due to their oncolytic properties.
- Vaccinia virus (VACV) and myxoma virus (MYXV) are key poxviruses explored as virotherapeutics, with VACV having advanced to clinical trials for various cancers.
- Myxoma virus (MYXV) shows potential beyond oncolysis, including immunotherapeutics and treating graft-versus-host diseases, also progressing towards clinical trials.
Purpose of the Study:
- To provide a guide for engineering poxvirus vectors for therapeutic transgene expression.
- To outline methods for producing viral preparations for preclinical studies.
- To highlight the unique engineering processes for poxvirus vectors compared to other DNA virus vectors.
Main Methods:
- Genetic engineering of poxvirus vectors (VACV and MYXV) to express therapeutic transgenes.
- Production of viral preparations for preclinical research.
- Discussion of poxvirus vector engineering distinct from other DNA viruses like herpesviruses.
Main Results:
- Poxvirus vectors, VACV and MYXV, demonstrate significant potential as oncolytic agents and for broader therapeutic applications.
- VACV has shown success in early-phase clinical trials for cancer therapy.
- MYXV is being explored for novel therapeutic uses and is advancing into clinical trials.
Conclusions:
- Poxvirus vectors offer a versatile platform for developing novel therapeutics, particularly in oncology and immunology.
- The genetic engineering of poxvirus vectors is crucial for tailoring them to specific therapeutic needs.
- This work serves as a foundational guide for researchers in the field of poxvirus-based virotherapeutics.
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