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Microbes & Immunity Genetic therapy with HSV-1 vectors
Figure 5. Radiation enhances viral replication and promotes the lysis of tumor cells
Abbreviation: TCR: T cell receptor.
Amplicons have already been used as vaccine vectors for clinical trials. To improve the safety of clinical application,
human immunodeficiency virus, intracellular bacteria, the UL41 gene was further deleted, and the sensitivity of
80
79
and neuropathogenic agents (Alzheimer’s disease and this derived virus to ACV, named d106S, was improved
prion dysregulation). 36,81 Amplicons have been successfully further. 89
used to carry all the genes of the mouse leukemia virus
(MoMLV) vector and, therefore, rescue retroviruses 5.3. Treatment of chronic pain
integrated into the cellular genome, expressing structural The treatment of cancer pain has long been a medical
82
83
proteins or non-structural proteins of Hepatitis C virus. problem that has an impact on human health and
84
Interestingly, the use of amplicons as carriers of cytokines social development and has become the second most
could constitute a research strategy for cancer vaccines. common disease after upper respiratory tract infection
Virus replication is necessary for efficient antigens to in North America. Although many types of pain can be
elicit robust immune responses. However, some non- managed pharmacologically, the drug affects the nervous
replicating vaccines, including replication-deficient HSV- system, causing sedation, irritability, anxiety, respiratory
1, elicit immune responses. 85,86 These viruses can still infect depression, and non-neural sites, resulting in urinary
host tissues but cause relatively low cytotoxicity, which retention, constipation, and addiction and tolerance, all of
may be related to their inability to replicate and spread in which limit the use of the drug.
the host. In an antigen model, ICP4, ICP22, and ICP27 null Transgenic viral vectors have the advantages of high
HSV-1 carrying ovalbumin (OVA) protected against lethal transfection efficiency and stable and lasting expression of
effects triggered by OVA expressed by monocytes. In exogenous genes. When a non-toxic replication-deficient
87
addition, HSV-1, a mutant lacking ICP27 that carries Env viral vector is used, the target gene is introduced into the
and Nef antigens of simian immunodeficiency virus (SIV) CNS, which is expected to achieve significant, stable, and
and infects rhesus macaques, effectively protects against lasting expression for treatment.
mucosal destruction triggered by the highly pathogenic The HSV-1-mediated proenkephalin gene (hPPE)
SIV mac239. 88
90
has been used to treat chronic pain. Wilson et al.
HSV-1-derived virus d106, which lacks multiple IE used a recombinant viral HSV vector carrying the
genes and has good immunogenicity and protective ability hPPE gene under the control of the HCMV promoter,
in rhesus monkey models, has been developed into a and immunohistochemical methods revealed that the
27
vaccine vector for the treatment of AIDS and has entered expression of hPPE in the spinal dorsal horn and dorsal
Volume 2 Issue 2 (2025) 27 doi: 10.36922/mi.7947

