Applications of Virus Vector–Mediated Gene Therapy in China

Lin, Qiong; Deng-gao, Wang; Zhang, Zhu-Qin; Liu, De-Pei

doi:10.1089/hum.2017.238

Cited by 5 publications

(3 citation statements)

References 113 publications

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“…Ad vectors have been studied extensively in tumor therapy trials 1 , 2 . In addition to the use of a conditionally-replicative Ad vector for head and neck cancer in China 3 , recent approval of an oncolytic herpesvirus-based treatment by the US Food and Drug Administration (FDA) raises optimism on the potential of viral vectors in cancer therapy 4 .…”

Section: Introductionmentioning

confidence: 99%

Enhancement of adenovirus infection and adenoviral vector-mediated gene delivery by bromodomain inhibitor JQ1

et al. 2018

Sci Rep

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Adenovirus-based vectors are among the most commonly used platforms for gene delivery and gene therapy studies. One of the obstacles for potential application is dose-related toxicity. We show here that adenovirus infection and Ad-mediated gene delivery can be enhanced by inhibitors of bromodomain and extra-terminal (BET) family proteins. We showed that JQ1, but not its inactive enantiomer (−)-JQ1, dose-dependently promoted Ad infection and Ad-mediated gene delivery in both epithelial and lymphocyte cells. Given orally, JQ1 also enhanced transgene expression in a murine tumor model. Inhibitors of histone deacetylases (HDACi) are among the commonly reported small molecule compounds which enhance Ad-mediated gene delivery. We found that JQ1 treatment did not cause histone acetylation nor expression of Ad attachment receptor CAR. Instead, JQ1 treatment induced an increase in BRD4 association with CDK9, a subunit of P-TEFb of transcription elongation. Concurrently, we showed that CDK9 inhibition blocked Ad infection and JQ1 enhancement on the infection. The study exemplifies the potentials of BET inhibitors like JQ1 in oncolytic virotherapy.

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Section: Introductionmentioning

confidence: 99%

Enhancement of adenovirus infection and adenoviral vector-mediated gene delivery by bromodomain inhibitor JQ1

et al. 2018

Sci Rep

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“…Although the concept of gene therapy has been around for decades, clinical research only began in 1990 at the National Institutes of Health (Friedmann 1992), where a clinical study of a rare immunodeficiency disorder was conducted. Recently, gene therapy has begun to emerge as a medical research hotspot and clinical studies have been conducted for a wide range of diseases, including cancer (Culver and Blaese 1994), monogenic inherited disease (Tucci et al 2021), infectious disease (Peterson and Kiem 2018;Lin et al 2018), neurodegenerative disease (Sun and Roy 2021) and other diseases (Wolf, Mitalipov, and Mitalipov 2019).…”

Section: Introductionmentioning

confidence: 99%

Optimization of multiplicity of infection and serum concentration to improve the titer of adenovirus by "design of experiments"

Zhou

Tang

Han

et al. 2023

Preprint

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Objective: To improve the adenovirus titer by optimizing the existing adenovirus-dependent HEK293 host cell expansion and replication experiments through a “design of experiments” (DoE) approach. Methods: Various concentrations of host HEK293 cells were infected with a different multiplicity of infection multiplicity of infection(MOI) of adenovirus using optimal experimental conditions, and the titers were detected using an adenovirus titer detection kit to evaluate the optimization effect. Results: Using DoE, we found that a serum concentration of 2.2%-2.4% and a MOI of 2.3-2.5 could maximize the adenovirus titers. Conclusion: Optimization of the experimental system of adenovirus culture using DoE could significantly shorten the production time and improve the titer of adenoviruses, providing an experimental basis for the current study and the subsequent expansion of production experiments.

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“…Clinical trial results 4,5 showed that rAd-p53 is effective against a variety of malignancies, including colon, glioma, lung, ovarian, and head and neck tumors. [6][7][8] We published an article on the clinical treatment of rAd-p53, 9 evaluated the efficacy of rAd-p53 (Gendicine Ò ) followed by chemotherapy in the treatment of uterine sarcoma.…”

Section: Introductionmentioning

confidence: 99%

Investigation on the Genomic Characterization of Uterine Sarcoma for rAd-p53 Combined with Chemotherapy Treatment

Wang

et al. 2020

Human Gene Therapy

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The aim is to investigate the genomic characterization of uterine sarcoma for rAd-p53 (Gendicine Ò) combined with chemotherapy treatment. We recently published an article on 12 cases of uterine sarcomas, which were treated with rAd-p53 combined with chemotherapy. We found that rAd-p53 combined with chemotherapy is effective for various uterine sarcomas. Pretreatment pathological specimens of four uterine sarcoma patients were collected from the above recent clinical research and numbered 1-4A/B. Tumor samples were subjected to targeted sequencing by using a 416 genes panel. We profiled the mutation spectrum and tumor mutation burden in the tumors, identified mutated genes, and explored their gene function. We also verified the p53 protein expression using immunohistochemistry. We identified a total of 30 mutated genes that were found from the next-generation sequencing test results. The average number of mutated genes was up to seven in the five samples. TP53 gene was mutated in two of the four patients, No. 1 and No. 4B. They are c.C833G (p.P278R) missense mutation and a point mutation (C141*) that result in a premature stop codon. We did not find a mutated TP53 gene in the other two cases, but we identified mutated genes, including CREBBP, LYN, CDKN2A, and JAK2, which were located upstream of the TP53 gene; they may have an impact on TP53. We also identified 11 additional genes which are involved in p53-related signaling pathways or have interaction with p53. Compared to solid tumor mutational burden (TMB) distribution, none of their TMB was ranking in the top 25%. Mutant p53 protein expression was positive in two specimens. Our results demonstrated that the TP53 signaling pathway plays an important role in uterine sarcoma tumorigenesis. TP53 and the upstream genes such as CREBBP, LYN, CDKN2A, and JAK2 may be involved in the genomic characterization for rAd-p53 (Gendicine) combined with chemotherapy in uterine sarcoma. Besides, the average amount of mutated genes from every patient is large.

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Applications of Virus Vector–Mediated Gene Therapy in China

Cited by 5 publications

References 113 publications

Enhancement of adenovirus infection and adenoviral vector-mediated gene delivery by bromodomain inhibitor JQ1

Enhancement of adenovirus infection and adenoviral vector-mediated gene delivery by bromodomain inhibitor JQ1

Optimization of multiplicity of infection and serum concentration to improve the titer of adenovirus by "design of experiments"

Investigation on the Genomic Characterization of Uterine Sarcoma for rAd-p53 Combined with Chemotherapy Treatment

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