Abstract:
:Vaccinia virus (VACV) was successfully used as a vaccine in the smallpox eradication campaign. Since then, it has been widely used in the development of vaccine and therapeutic vectors. However, methods of generating and purifying recombinant VACVs (rVACVs) are often time-consuming, cumbersome, and in some cases require specialized cell lines or equipment. Here, we describe a novel EPPIC (Efficient Purification by Parental Inducer Constraint) platform for the rapid generation of rVACVs using a replication-inducible VACV (vIND) as a parental virus for homologous recombination. Purification of the rVACV from the parental vIND is achieved by two serial passages in the absence of inducer (i.e., parental inducer "constraint") in standard laboratory cell lines, without the need for specialized equipment, within 1 week. We determined the optimal conditions for homologous recombination and serial purification and generated a suite of vIND parental viruses to facilitate customization of the platform. Importantly, the EPPIC platform can be adapted to rapidly generate replication-deficient and replication-competent rVACVs expressing vaccine or therapeutic antigens, with or without screening markers, by simple modifications to a DNA shuttle vector, thus allowing the rapid development, updating, and refinement of personalized or custom vaccines and therapeutic vectors in a matter of days.
journal_name
Mol Ther Methods Clin Devjournal_title
Molecular therapy. Methods & clinical developmentauthors
Jasperse B,O'Connell CM,Wang Y,Verardi PHdoi
10.1016/j.omtm.2020.03.026subject
Has Abstractpub_date
2020-03-30 00:00:00pages
731-738issn
2329-0501pii
S2329-0501(20)30056-5journal_volume
17pub_type
杂志文章abstract::In vivo imaging of vector transgene expression would be particularly valuable for repetitive monitoring of therapy in the brain, where invasive tissue sampling is contraindicated. We evaluated adeno-associated virus vector expression of a dopamine-2 receptor (D2R) mutant (D2R80A) by positron emission tomography in the...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2014.16
更新日期:2014-06-04 00:00:00
abstract::Retroviral vectors, including those derived from gammaretroviruses and lentiviruses, have found their way into the clinical arena and demonstrated remarkable efficacy for the treatment of immunodeficiencies, leukodystrophies, and globinopathies. Despite these successes, gene therapy unfortunately also has had to face ...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章,评审
doi:10.1016/j.omtm.2017.10.002
更新日期:2017-10-05 00:00:00
abstract::Recombinant adeno-associated viral (rAAV) vectors have been widely used in human gene therapy. One major impediment to its broad application is the inability to produce high-quality vectors in mass quantity. Here, an efficient and scalable suspension cell culture system for the production of rAAV vectors is described....
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2017.11.002
更新日期:2017-11-07 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2017.08.007
更新日期:2017-09-07 00:00:00
abstract::Current cell processing technologies for gene and cell therapies are often slow, expensive, labor intensive and are compromised by high cell losses and poor selectivity thus limiting the efficacy and availability of clinical cell therapies. We employ cell-specific on-demand mechanical intracellular impact from laser p...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2016.12
更新日期:2016-03-16 00:00:00
abstract::Spinal muscular atrophy (SMA) is a devastating childhood motor neuron disease. SMA is caused by mutations in the survival motor neuron gene (SMN1), leading to reduced levels of SMN protein in the CNS. The actin-binding protein plastin 3 (PLS3) has been reported as a modifier for SMA, making it a potential therapeutic ...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2018.01.007
更新日期:2018-01-31 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2020.09.004
更新日期:2020-09-16 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2019.01.014
更新日期:2019-02-07 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2016.83
更新日期:2016-12-07 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2020.04.023
更新日期:2020-05-04 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2020.03.001
更新日期:2020-03-14 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2018.07.008
更新日期:2018-07-21 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2019.08.013
更新日期:2019-09-06 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2019.09.004
更新日期:2019-09-18 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2020.07.012
更新日期:2020-07-15 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2020.09.017
更新日期:2020-10-01 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2018.10.012
更新日期:2018-12-05 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2018.03.002
更新日期:2018-03-10 00:00:00
abstract::[This corrects the article DOI: 10.1038/mtm.2015.16.]. ...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 已发布勘误
doi:10.1038/mtm.2016.32
更新日期:2016-05-25 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2018.04.004
更新日期:2018-04-12 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2018.10.016
更新日期:2018-11-01 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2014.61
更新日期:2015-04-01 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2016.12.004
更新日期:2016-12-24 00:00:00
abstract::Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB [MPS IIIB]) is a lysosomal storage disorder primarily affecting the brain that is caused by a deficiency in the enzyme α-N-acetylglucosaminidase (NAGLU), leading to intralysosomal accumulation of heparan sulfate. There are currently no treatments for this dis...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2018.06.005
更新日期:2018-07-23 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章,评审
doi:10.1016/j.omtm.2019.10.010
更新日期:2019-10-31 00:00:00
abstract::Integration of new DNA into cellular genomes mediates replication of retroviruses and transposons; integration reactions have also been adapted for use in human gene therapy. Tracking the distributions of integration sites is important to characterize populations of transduced cells and to monitor potential outgrow of...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2016.11.002
更新日期:2016-12-18 00:00:00
abstract::Adeno-associated virus (AAV) vector serotypes vary in their ability to transduce hepatocytes from different species. Chimeric mouse models harboring human hepatocytes have shown translational promise for liver-directed gene therapies. However, many variables that influence human hepatocyte transduction and transgene e...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2020.05.033
更新日期:2020-06-02 00:00:00
abstract::Gene replacement therapies, like organ and cell transplantation are likely to introduce neo-antigens that elicit rejection via humoral and/or effector T cell immune responses. Nonetheless, thanks to an ever growing body of pre-clinical studies it is now well accepted that gene transfer protocols can be specifically de...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2014.13
更新日期:2014-04-30 00:00:00
abstract::Pancreatic cancer is an aggressive malignancy that often goes undiagnosed in the early stages. Non-invasive, early, and accurate diagnosis is therefore undoubtedly the "holy grail" of pancreatic cancer research. However, despite extensive research efforts, there is no definitive biomarker for this cancer. Previously, ...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2019.08.016
更新日期:2019-09-12 00:00:00
abstract::Crigler-Najjar syndrome is a severe metabolic disease of the liver due to a reduced activity of the UDP Glucuronosyltransferase 1A1 (UGT1A1) enzyme. In an effort to translate to the clinic an adeno-associated virus vector mediated liver gene transfer approach to treat Crigler-Najjar syndrome, we developed and optimize...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2016.49
更新日期:2016-07-20 00:00:00