Advancements in the design and scalable production of viral gene transfer vectors

Sharon, David; Kamen, Amine

doi:10.1002/bit.26461

Cited by 54 publications

(51 citation statements)

References 126 publications

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“…Owing to the close relation between the emergence of tumor resistance and the tumor microenvironment, as well as the intratumoral heterogeneity and complexity, we sought further verification using drug-resistant TNBC xenografts as an in vivo model of chemoresistance seen in the clinic. First, we needed to introduce ectogenic hsamiRNA-143-3p with a recombinant lentivirus that leads to efficient transfection and sustained expression of the desired gene to host cells [ 23 ]. Regrettably, relying on insertional mutagenesis of lentivirus-expression vectors to induce oncogenesis poses a safety risk and may cause abnormal expression of the transgene in adjacent normal tissues [ 24 ], therefore, it is crucial to ensure correct targeting of the recombinant lentivirus.…”

Section: Discussionmentioning

confidence: 99%

Hsa-miRNA-143-3p Reverses Multidrug Resistance of Triple-Negative Breast Cancer by Inhibiting the Expression of Its Target Protein Cytokine-Induced Apoptosis Inhibitor 1In Vivo

Deng

Hao

et al. 2018

J Breast Cancer

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PurposeMultidrug resistance (MDR) remains a major obstacle in the treatment of triple-negative breast cancer (TNBC) with conventional chemotherapeutic agents. A previous study demonstrated that hsa-miRNA-143-3p plays a vital role in drug resistance of TNBC. Downregulation of hsa-miRNA-143-3p upregulated the expression of its target protein cytokine-induced apoptosis inhibitor 1 (CIAPIN1) in order to activate MDR, while upregulation of hsa-miRNA-143-3p effectively enhances the sensitivity of drug-resistant TNBC cells to chemotherapeutics. The present study aimed to further verify these findings in vivo.MethodsWe established a hypodermic tumor nude mice model using paclitaxel-resistant TNBC cells. We expressed ectopic hsa-miRNA-143-3p under the control of a breast cancer-specific human mammaglobin promoter that guided the efficient expression of exogenous hsa-miRNA-143-3p only in breast cancer cells. Thereafter, we overexpressed hsa-miRNA-143-3p in xenografts using a recombinant virus system and quantified the expression of hsa-miRNA-143-3p, CIAPIN1 protein, and proteins encoded by related functional genes by western blot.ResultsWe successfully completed the prospective exploration of the intravenous virus injection pattern from extensive expression to targeted expression. The overexpression of hsa-miRNA-143-3p significantly alleviated chemoresistance of TNBC by inhibiting viability. In addition, we observed that the expression of CIAPIN1 as a hsa-miRNA-143-3p target protein was remarkably decreased.ConclusionWe partly illustrated the mechanism underlying the hsa-miRNA-143-3p/CIAPIN1 drug resistance pathway. HsamiRNA-143-3p as a tumor suppressive microRNA may be a novel target to effectively reverse MDR of TNBC in vivo.

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Section: Discussionmentioning

confidence: 99%

Hsa-miRNA-143-3p Reverses Multidrug Resistance of Triple-Negative Breast Cancer by Inhibiting the Expression of Its Target Protein Cytokine-Induced Apoptosis Inhibitor 1In Vivo

Deng

Hao

et al. 2018

J Breast Cancer

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“…29,56 Although AAV vectors generally do not integrate into host genomes, they may induce long-term gene expression in non-dividing cells (eg, neurons) and are primarily being used to develop gene therapy treatments of monogenic hereditary disorders. 29,56 Thus, gene therapy product safety risks are inherent to the parent wild-type virus, as well as considering the potential toxicity of the desired transgene it contains. 4,48,54 The NIH and WHO guidelines categorize wild-type infectious agents into RGs for laboratory research; however, these may be adapted for clinical application.…”

Section: Different Viral Vectors Have Different Levels Of Riskmentioning

confidence: 99%

Gene Replacement Therapy: A Primer for the Health-system Pharmacist

Petrich

Marchese

Jenkins³

et al. 2019

Journal of Pharmacy Practice

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Purpose:Comprehensive review of gene replacement therapy with guidance and expert opinion on handling and administration for pharmacists.Summary:There are currently ∼2600 gene therapy clinical trials worldwide and 4 Food and Drug Administration (FDA)-approved gene therapy products available in the United States. Gene therapy and its handling are different from other drugs; however, there is a lack of guidance from the National Institutes of Health (NIH), FDA, Centers for Disease Control and Prevention (CDC), World Health Organization (WHO), and professional associations regarding their pharmaceutical application. Although the NIH stratifies the backbone biologicals of viral vectors in gene therapies into risk groups, incomplete information regarding minimization of exposure and reduction of risk exists. In the absence of defined guidance, individual institutions develop their own policies and procedures, which often differ and are often outdated. This review provides expert opinion on the role of pharmacists in institutional preparedness, as well as gene therapy handling and administration. A suggested infrastructural model for gene replacement therapy handling is described, including requisite equipment acquisition and standard operating procedure development. Personnel, patient, and caregiver education and training are discussed.Conclusion:Pharmacists have a key role in the proper handling and general management of gene replacement therapies, identifying risk level, establishing infrastructure, and developing adequate policies and protocols, particularly in the absence of consensus guidelines for the handling and transport of gene replacement therapies.

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“…39 The viral vectors were the first molecular tools for gene transduction into human somatic cells 40 and are now widely investigated in clinical translational research because of their incomparable superiority over nonviral vectors with respect to cell invasion and the insertion of the genetic materials. 41 However, much risk still exists regarding the immune response to viruses and genome manipulation. 42 By contrast, non-viral vectors have no such major concerns as a result of their higher safety, especially for direct in vivo administration.…”

Section: Delivery Vectorsmentioning

confidence: 99%

Clinical translation of gene medicine

Wang

Zhou

et al. 2019

The Journal of Gene Medicine

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Gene therapy has recently witnessed accelerated progress as a new therapeutic strategy with the potential to treat a range of inherited and acquired diseases. Billions of dollars have been invested in basic and clinical research on gene medicine, with ongoing clinical trials focused on cancer, monogenic diseases, cardiovascular diseases and other refractory diseases. Advances addressing the inherent challenges of gene therapy, particularly those related to retaining the delivery efficacy and minimizing unwanted immune responses, provide the basis for the widespread clinical application of gene medicine. Several types of genes delivered by viral or non‐viral delivery vectors have demonstrated encouraging results in both animals and humans. As augmented by clinical indications, gene medicine techniques have rapidly become a promising alternative to conventional therapeutic strategies because of their better clinical benefit and lower toxicities. Their application in the clinic has been extensive as a result of the approval of many gene therapy drugs in recent years. In this review, we provide a comprehensive overview of the clinical translation of gene medicine, focusing on the key events and latest progress made regarding clinical gene therapy products. We also discuss the gene types and non‐viral materials with respect to developing gene therapeutics in clinical trials.

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Advancements in the design and scalable production of viral gene transfer vectors

Cited by 54 publications

References 126 publications

Hsa-miRNA-143-3p Reverses Multidrug Resistance of Triple-Negative Breast Cancer by Inhibiting the Expression of Its Target Protein Cytokine-Induced Apoptosis Inhibitor 1In Vivo

Hsa-miRNA-143-3p Reverses Multidrug Resistance of Triple-Negative Breast Cancer by Inhibiting the Expression of Its Target Protein Cytokine-Induced Apoptosis Inhibitor 1In Vivo

Gene Replacement Therapy: A Primer for the Health-system Pharmacist

Clinical translation of gene medicine

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