Oncolytic Herpes Simplex Viral Therapy: A Stride toward Selective Targeting of Cancer Cells

Sanchala, Dhaval; Bhatt, Lokesh Kumar; Prabhavalkar, Kedar

doi:10.3389/fphar.2017.00270

Cited by 33 publications

(21 citation statements)

References 62 publications

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“…The method described here could become a common approach for manipulating other herpesviruses or DNA viruses in the future; currently, it is useful for vaccine development (14), gene function exploration (19), and oncolytic virus design (38).…”

Section: Discussionmentioning

confidence: 99%

CRISPR/Cas9‐mediated 2‐sgRNA cleavage facilitates Pseudorabies virus editing

et al. 2018

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Several groups have used CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) for DNA virus editing. In most cases, one single-guide RNA (sgRNA) is used, which produces inconsistencies in gene editing. In this study, we used a swine herpesvirus, pseudorabies virus, as a model to systematically explore the application of CRISPR/Cas9 in DNA virus editing. In our current report, we demonstrated that cotransfection of 2 sgRNAs and a viral genome resulted in significantly better knockout efficiency than the transfection-infection-based approach. This method could result in 100% knockout of ≤3500 bp of viral nonessential large fragments. Furthermore, knockin efficiency was significantly improved by using 2 sgRNAs and was also correlated with the number of background viruses. We also demonstrated that the background viruses were all 2-sgRNA-mediated knockout mutants. Finally, this study demonstrated that the efficacy of gene knockin is determined by the replicative kinetics of background viruses. We propose that CRISPR/Cas9 coupled with 2 sgRNAs creates a powerful tool for DNA virus editing and offers great potential for future applications.-Tang, Y.-D., Guo, J.-C., Wang, T.-Y., Zhao, K., Liu, J.-T., Gao, J.-C., Tian, Z.-J., An, T.-Q., Cai, X.-H. CRISPR/Cas9-mediated 2-sgRNA cleavage facilitates pseudorabies virus editing.

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Section: Discussionmentioning

confidence: 99%

CRISPR/Cas9‐mediated 2‐sgRNA cleavage facilitates Pseudorabies virus editing

et al. 2018

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“…However there is no direct evidence that herpes simplex virus causes tumors, so that HSV can be engineered as oncolytic HSV (oHSV) to combat cancer [6][7][8][9]. In oHSVs, HSV can infect a variety of host cells to meet the needs of oncolytic virus therapy, and various forms of transgenic vectors have been developed for cancer therapy [10,11]. For example, the most advanced oHSVs T-Vec (Talimogene laherparepvec), G207, 1716, G47Δ and HF10 have been evaluated in clinical trials for their benefits in treating advanced cancers such as melanoma, glioma, head and neck cancer and breast cancer [12].…”

Section: Ivyspringmentioning

confidence: 99%

Transcriptional Regulation of Latency-Associated Transcripts (LATs) of Herpes Simplex Viruses

Zhang

Xin

Zhang³

et al. 2020

J. Cancer

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Herpes simplex viruses (HSVs) cause cold sores and genital herpes and can establish lifelong latent infection in neurons. An engineered oncolytic HSV (oHSV) has recently been approved to treat tumors in clinics. HSV latency-associated transcripts (LATs) are associated with the latent infection, but LAT transcriptional regulation was seldom reported. For a better treatment of HSV infection and tumors, here we sequenced the LAT encoding DNA and LAT transcription regulatory region of our recently isolated new strain HSV-1-LXMW and did comparative analysis of the sequences together with those of other four HSV-1 and two HSV-2 strains. Phylogenetic analysis of LATs revealed that HSV-1-LXMW is evolutionarily close to HSV-1-17 from MRC University, Glasgow, UK. For the first time, Using a weight matrix-based program Match and multi-sequences alignment of the 6 HSV strains, we identified HSV LAT transcription regulatory sequences that bind to 9 transcription factors: AP-1, C-REL, Comp1, E2F, Hairy, HFH-3, Kr, TCF11/MAFG, v-Myb. Interestingly, these transcription regulatory sequences and factors are either conserved or unique among LATs of HSV-1 and HSV-2, suggesting they are potentially functional. Furthermore, literature analysis found that the transcription factors v-myb and AP-1 family member JunD are functional in regulating HSV gene transcription, including LAT transcription. For the first time, we discovered seven novel transcription factors and their corresponding transcription regulatory sequences of HSV LATs. Based on our findings and other reports, we proposed potential mechanisms of the initiation and maintenance of HSV latent infection. Our findings may have significant implication in our understanding of HSV latency and engineering of better oncolytic HSVs.

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“…The buildup of progeny results in lysis of the cells and infection of neighboring cancer cells [3]. This approach is effective for solid tumors, as viral delivery may be accomplished through direct intratumoral injections, resulting in direct killing of the malignant cells without producing severe systemic side effects or unwanted hepatic degradation of the virus, which may occur with systemic injection [4]. As a result of viral-mediated tumor cell lysis, pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and tumor-associated antigens (TAA) are released.…”

Section: Oncolytic Virus-based Therapymentioning

confidence: 99%

Immunotherapy in Pediatric Solid Tumors—A Systematic Review

Marayati

Quinn

Beierle

2019

Cancers

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Despite advances in the treatment of many pediatric solid tumors, children with aggressive and high-risk disease continue to have a dismal prognosis. For those presenting with metastatic or recurrent disease, multiple rounds of intensified chemotherapy and radiation are the typical course of action, but more often than not, this fails to control the progression of the disease. Thus, new therapeutics are desperately needed to improve the outcomes for these children. Recent advances in our understanding of both the immune system’s biology and its interaction with tumors have led to the development of novel immunotherapeutics as alternative treatment options for these aggressive malignancies. Immunotherapeutic approaches have shown promising results for pediatric solid tumors in early clinical trials, but challenges remain concerning safety and anti-tumor efficacy. In this review, we aim to discuss and summarize the main classes of immunotherapeutics used to treat pediatric solid tumors.

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Oncolytic Herpes Simplex Viral Therapy: A Stride toward Selective Targeting of Cancer Cells

Cited by 33 publications

References 62 publications

CRISPR/Cas9‐mediated 2‐sgRNA cleavage facilitates Pseudorabies virus editing

CRISPR/Cas9‐mediated 2‐sgRNA cleavage facilitates Pseudorabies virus editing

Transcriptional Regulation of Latency-Associated Transcripts (LATs) of Herpes Simplex Viruses

Immunotherapy in Pediatric Solid Tumors—A Systematic Review

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