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Microbes & Immunity Genetic therapy with HSV-1 vectors

root ganglion (DRG) inhibited the sensitivity of C-fibers Neurological lesions are common, and there are no
to capsaicin (low stimulation intensity) and/or Aδ to specific treatments available. With the development of
dimethylsulfoxide (high stimulation intensity) stimulation genetic engineering, HSV-1-derived vectors have been
and significantly prolonged the latency of the leg gradually applied in the treatment of neurological lesions.
withdrawal response in rats, suggesting that the function HSV-1 can infect post-mitotic neurons, retrogradely enter
of sensory neurons can be altered by the transfection of the the CNS after infection of peripheral nerves, and establish
target gene with the viral vector. Using a formalin test, they latent infection; thus, HSV-1 can be used as a vehicle
inoculated rats with HSV-1 deletion of the proenkephalin for exogenous genes. 94-96 HSV-1 neurotoxicity mainly
gene (ICP4 removed) in the soles of the feet and reported stems from non-essential genes, so investigators have
that vector-mediated enkephalin expression directly used genetic engineering technology to knock out these
produced antinociceptive effects against formalin-induced non-essential genes to attenuate or ameliorate HSV-1
inflammatory pain stimulation for up to 4 weeks and that neurotoxicity.
reinoculation of the vector again produced antinociceptive HSV-1-derived viruses are poorly initiated and can
effects. only be expressed for short periods in neural cells through
Goss et al. injected osteolytic osteosarcoma cells into exogenous promoters. Investigators are working to
91
the bone marrow cavity of the right femur of mice and construct a model that uses latency-associated transcript
inoculated them with the hPPE vector 7 days later, and the promoters to express exogenous genes by investigating
control group was inoculated with the LacZ-expressing latency in the viral life cycle. HSV-1-derived vectors are
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vector; the authors reported that mice inoculated with very important for treating neurological diseases such as
hPPE had significantly reduced naltrexone-reversible chronic pain, but they are still in the early stage of clinical
pain-related behaviors, as assessed in terms of open-field trials, and a series of problems, such as the stability and
motor activity, indicating that HSV-1-mediated gene targeting of transgene expression and immune strategies to
therapy for hPPE also significantly attenuated nociception cope with the host, need to be solved.
in cancer pain. HSV-1-based non-replicative vectors have
also been applied to treat pain resulting from Parkinson’s Acknowledgments
92
disease and spinal cord injury. In addition, the use of None.
these viral vectors to transfer vascular endothelial growth
factor into the DRG of mice with diabetic neuropathy is Funding
also an efficient treatment. 93
This work was supported by the National Natural Science
HSV-1-derived vectors have great importance for Foundation of China (82072263).
treating chronic pain, but gene therapy through these viral
vectors is still in the early stage of clinical trials, and a series Conflict of interest
of problems remain to be solved, such as the neurotoxicity Chunfu Zheng is an Editorial Board Member of this
of the viral vector, neuronal lysis caused by viral proteins, journal but was not in any way involved in the editorial and
selection of the best target gene, stability and targeting of peer-review process conducted for this paper, directly or
transgene expression, and immune strategies to cope with indirectly. The author also declared that he has no known
the host. competing financial interests or personal relationships that
6. Summary could have influenced the work reported in this paper.
HSV-1-derived vectors have already been applied in Author contributions
cancer therapy, gene delivery, and vaccine vectors. Highly This is a single-authored article.
attenuated HSV-1 can selectively invade and kill a variety
of tumor cells safely and can be effectively regulated by Ethics approval and consent to participate
drugs. The successful treatment of patients with head Not applicable.
and neck cancer via the use of transgenic HSV-1 vectors
combined with radiotherapy and chemotherapy effectively Consent for publication
inhibits cancer recurrence after tumor resection surgery.
HSV-1-derived vectors have broad application prospects in Not applicable.
oncolytic therapy. The HSV-1 vector has a high transfection
rate in DC cells, can load multiple antigen genes at the Availability of data
same time, and has very broad potential as a gene vaccine. Not applicable.

Volume 2 Issue 2 (2025) 28 doi: 10.36922/mi.7947