Minicircle DNA vectors devoid of bacterial DNA result in persistent and high-level transgene expression in vivo

Chen, Zhiying; He, Cheng-Yi; Ehrhardt, Anja; Kay, Mark A.

doi:10.1016/s1525-0016(03)00168-0

Cited by 429 publications

(438 citation statements)

References 24 publications

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“…Non-viral vectors can simply be injected via the tail vein in rodent models, with many innovations developed to increase transgene expression by minimizing the bacterial backbone of plasmid DNA, including the use of minicircles and mini-intronic plasmids [54,55]. While non-targeting vectors have been used successfully to transduce hepatocytes, using a virus with a defined hepatocyte-specific tropism can both improve specificity and efficacy.…”

Section: A Brief History Of In-vivo Gene Therapymentioning

confidence: 99%

Lessons learned from lung and liver in-vivo gene therapy: implications for the future

Haasteren

Hyde

Gill

2018

Expert Opinion on Biological Therapy

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Introduction: Ex-vivo gene therapy has had significant clinical impact over the last couple of years and in-vivo gene therapy products are being approved for clinical use. Gene therapy and gene editing approaches have huge potential to treat genetic disease and chronic illness. Areas covered: This article provides a review of in-vivo approaches for gene therapy in the lung and liver, exploiting non-viral and viral vectors with varying serotypes and pseudotypes to target-specific cells. Antibody responses inhibiting viral vectors continue to constrain effective repeat administration. Lessons learned from ex-vivo gene therapy and genome editing are also discussed. Expert opinion: The fields of lung and liver in-vivo gene therapy are thriving and a comparison highlights obstacles and opportunities for both. Overcoming immunological issues associated with repeated administration of viral vectors remains a key challenge. The addition of targeted small molecules in combination with viral vectors may offer one solution. A substantial bottleneck to the widespread adoption of in-vivo gene therapy is how to ensure sufficient capacity for clinical-grade vector production. In the future, the exploitation of gene editing approaches for in-vivo disease treatment may facilitate the resurgence of non-viral gene transfer approaches, which tend to be eclipsed by more efficient viral vectors.

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Section: A Brief History Of In-vivo Gene Therapymentioning

confidence: 99%

Lessons learned from lung and liver in-vivo gene therapy: implications for the future

Haasteren

Hyde

Gill

2018

Expert Opinion on Biological Therapy

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“…Guidance on the use of medicinal products for gene transfer advise great care in the use of selection markers used in such products due to their significant potential to impact human therapy. This is especially pertinent to the presence of antibiotic resistance genes since these can restrict more general treatment options [30,46,56,57]. Indeed, medical and clinical regulatory bodies advise limiting the use of antibiotic resistance genes for therapy where feasible [58].…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Part I: Minicircle vector technology limits DNA size restrictions on ex vivo gene delivery using nanoparticle vectors: Overcoming a translational barrier in neural stem cell therapy

Fernandes

Chari

2016

Journal of Controlled Release

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Please cite this article as: Alinda R. Fernandes, Divya M. Chari, Part I: Minicircle vector technology limits DNA size restrictions on ex vivo gene delivery using nanoparticle vectors: Overcoming a translational barrier in neural stem cell therapy, Journal of Controlled Release (2016Release ( ), doi: 10.1016Release ( /j.jconrel.2016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT

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“…We are currently exploring the possibility of obtaining mini-circle DNA vectors devoid of bacterial DNA, since these have recently been shown to result in persistent and high-level transgene expression. 26 Although plasmid DNA was used in this study, an electroporation-based approach is broadly capable of safely and effectively delivering other molecules to cells as well. For instance, we have previously shown that this approach can be used to deliver protein/peptide antigens, antibodies, oligonucleotides, siRNA, and large macromolecules, such as Dextran (MW 500 kDa), efficiently and safely to many other cell types.…”

Section: Discussionmentioning

confidence: 99%

Rapid, in vivo, evaluation of antiangiogenic and antineoplastic gene products by nonviral transfection of tumor cells

et al. 2004

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Using a nonviral, electroporation-based gene transfection approach, we demonstrate the efficient and consistent transfection of two poorly immunogenic tumor cell lines: B16F10 melanoma and renal carcinoma (RENCA). Three genes, IL-12, angiostatin (AS), and an endostatin:angiostatin fusion protein (ES:AS) were subcloned into a DNA plasmid containing EBNA1-OriP, which was then transfected into B16F10 and RENCA cells. Significant levels of protein were secreted into the culture supernatants of transfected cells in vitro. Transfected tumor cells were injected subcutaneously into mice. All the three transgenes were capable of significantly delaying and reducing the formation of primary B16F10 and RENCA tumors, as well as B16F10 lung metastases. By day 11 postinjection, all control mice that received either mock-transfected or empty vector DNA-transfected B16F10 tumor cells had developed large primary tumors. In contrast, mice that received IL-12-transfected B16F10 cells did not develop appreciable tumors until day 17, and these were significantly smaller than controls. Similar results were observed for the RENCA model, in which only one of the IL-12 mice had developed tumors out to day 31. Expression of AS or ES:AS also significantly delayed and reduced primary tumors. Overall, ES:AS was more effective than AS alone. Furthermore, 25% of the AS mice and 33% of the ES:AS mice remained tumor-free at day 17, by which point all control mice had significant tumors. Mouse survival rates also correlated with the extent of tumor burden. Importantly, no lung metastases were detected in the lungs of mice that had received either AS or ES:AS-transfected B16F10 tumor cells and significantly fewer metastases were found in the IL-12 group. The consistency of our transfection results highlight the feasibility of directly electroporating tumor cells as a means to screen, identify, and validate in vivo potentially novel antiangiogenic and/or antineoplastic genes.

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Minicircle DNA vectors devoid of bacterial DNA result in persistent and high-level transgene expression in vivo

Cited by 429 publications

References 24 publications

Lessons learned from lung and liver in-vivo gene therapy: implications for the future

Lessons learned from lung and liver in-vivo gene therapy: implications for the future

Part I: Minicircle vector technology limits DNA size restrictions on ex vivo gene delivery using nanoparticle vectors: Overcoming a translational barrier in neural stem cell therapy

Rapid, in vivo, evaluation of antiangiogenic and antineoplastic gene products by nonviral transfection of tumor cells

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