abstract：:LAMA2-related muscular dystrophy (LAMA2 MD) is the most common and fatal form of early-onset congenital muscular dystrophies. Due to the large size of the laminin α2 cDNA and heterotrimeric structure of the protein, it is challenging to develop a gene-replacement therapy. Our group has developed a novel adeno-associat...

journal_title：Molecular therapy. Methods & clinical development

authors： Qiao C,Dai Y,Nikolova VD,Jin Q,Li J,Xiao B,Li J,Moy SS,Xiao X

更新日期：2018-01-31 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

authors： Wang Q,Wu Z,Zhang J,Firrman J,Wei H,Zhuang Z,Liu L,Miao L,Hu Y,Li D,Diao Y,Xiao W

更新日期：2017-11-07 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

authors： Biasco L,Rothe M,Büning H,Schambach A

更新日期：2017-10-05 00:00:00

abstract：:New methods to produce large numbers of myeloid progenitor cells, precursors to macrophages (MΦs), by maintaining Hoxb8 transcription factor activity1 has reinvigorated interest in MΦ cell therapies. We generated Hoxb8-dependent myeloid progenitors (HDPs) by transducing lineage-negative bone marrow cells with a consti...

journal_title：Molecular therapy. Methods & clinical development

authors： Lee S,Kivimäe S,Szoka FC

更新日期：2017-09-07 00:00:00

abstract：:The marketing approval of genetically engineered hematopoietic stem cells (HSCs) as the first-line therapy for the treatment of severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID) is a tribute to the substantial progress that has been made regarding HSC engineering in the past decade. Rep...

journal_title：Molecular therapy. Methods & clinical development

authors： Wang X,Rivière I

更新日期：2017-03-18 00:00:00

abstract：:Umbilical cord blood (CB) has emerged as an effective alternative donor source for hematopoietic stem cell transplantation. Despite this success, the prolonged duration of immune suppression following CB transplantation and the naiveté of CB T cells leave patients susceptible to viral infections. Adoptive transfer of ...

journal_title：Molecular therapy. Methods & clinical development

authors： Dave H,Luo M,Blaney JW,Patel S,Barese C,Cruz CR,Shpall EJ,Bollard CM,Hanley PJ

更新日期：2017-03-08 00:00:00

abstract：:Adeno-associated virus (AAV) vectors have emerged as a safe and efficient gene therapy platform. One complication is that a significant amount of empty particles have always been generated as impurities during AAV vector production. However, the effects of such particles on AAV vector performance remain unclear. Here ...

journal_title：Molecular therapy. Methods & clinical development

authors： Wang Q,Dong B,Pokiniewski KA,Firrman J,Wu Z,Chin MP,Chen X,Liu L,Xu R,Diao Y,Xiao W

更新日期：2016-12-24 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

authors： Sherman E,Nobles C,Berry CC,Six E,Wu Y,Dryga A,Malani N,Male F,Reddy S,Bailey A,Bittinger K,Everett JK,Caccavelli L,Drake MJ,Bates P,Hacein-Bey-Abina S,Cavazzana M,Bushman FD

更新日期：2016-12-18 00:00:00

abstract：:The tolerogenic hepatic microenvironment impedes clearance of viral infections but is an advantage in viral vector gene transfer, which often results in immune tolerance induction to transgene products. Although the underlying tolerance mechanism has been extensively studied, our understanding of antigen presentation ...

journal_title：Molecular therapy. Methods & clinical development

authors： Perrin GQ,Zolotukhin I,Sherman A,Biswas M,de Jong YP,Terhorst C,Davidoff AM,Herzog RW

更新日期：2016-12-07 00:00:00

abstract：:The advent of RNA-guided endonuclease (RGEN)-mediated gene editing, specifically via CRISPR/Cas9, has spurred intensive efforts to improve the efficiency of both RGEN delivery and targeted mutagenesis. The major viral vectors in use for delivery of Cas9 and its associated guide RNA, lentiviral and adeno-associated vir...

journal_title：Molecular therapy. Methods & clinical development

authors： Park A,Hong P,Won ST,Thibault PA,Vigant F,Oguntuyo KY,Taft JD,Lee B

更新日期：2016-08-24 00:00:00

abstract：:Pompe disease (PD) is a lysosomal disorder caused by acid α-glucosidase (GAA) deficiency. Progressive muscular weakness is the major symptom of PD, and enzyme replacement therapy can improve the clinical outcome. However, to achieve a better clinical outcome, alternative therapeutic strategies are being investigated, ...

journal_title：Molecular therapy. Methods & clinical development

authors： Sato Y,Kobayashi H,Higuchi T,Shimada Y,Ida H,Ohashi T

更新日期：2016-08-10 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

authors： Ronzitti G,Bortolussi G,van Dijk R,Collaud F,Charles S,Leborgne C,Vidal P,Martin S,Gjata B,Sola MS,van Wittenberghe L,Vignaud A,Veron P,Bosma PJ,Muro AF,Mingozzi F

更新日期：2016-07-20 00:00:00

abstract：:[This corrects the article DOI: 10.1038/mtm.2015.16.]. ...

journal_title：Molecular therapy. Methods & clinical development

authors： Palfi A,Chadderton N,O'Reilly M,Nagel-Wolfrum K,Wolfrum U,Bennett J,Humphries P,Kenna P,Millington-Ward S,Farrar J

更新日期：2016-05-25 00:00:00

abstract：:To date, gene therapy with transiently derived lentivectors has been very successful to cure rare infant genetic diseases. However, transient manufacturing is unfeasible to treat adult malignancies because large vector lots are required. By contrast, stable manufacturing is the best option for high-incidence diseases ...

journal_title：Molecular therapy. Methods & clinical development

authors： Marin V,Stornaiuolo A,Piovan C,Corna S,Bossi S,Pema M,Giuliani E,Scavullo C,Zucchelli E,Bordignon C,Rizzardi GP,Bovolenta C

更新日期：2016-05-11 00:00:00

abstract：:Rituximab is a mouse/human chimeric monoclonal antibody targeted toward CD20. It is efficient as first-line therapy of CD20-positive B-cell malignancies. However, a large fraction of treated patients relapse with rituximab-resistant disease. So far, only modest progress has been made in treatment options for rituximab...

journal_title：Molecular therapy. Methods & clinical development

authors： Richter M,Yumul R,Saydaminova K,Wang H,Gough M,Baldessari A,Cattaneo R,Lee F,Wang CH,Jang H,Astier A,Gopal A,Carter D,Lieber A

更新日期：2016-03-30 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

authors： Lukianova-Hleb EY,Yvon ES,Shpall EJ,Lapotko DO

更新日期：2016-03-16 00:00:00

abstract：:Osteoarthritis (OA) is a joint disease characterized by degeneration of the articular cartilage, subchondral bone remodeling, and secondary inflammation. It is among the top three causes of chronic disability, and currently there are no treatment options to prevent disease progression. The localized nature of OA makes...

journal_title：Molecular therapy. Methods & clinical development

authors： Ruan MZ,Cerullo V,Cela R,Clarke C,Lundgren-Akerlund E,Barry MA,Lee BH

更新日期：2016-03-09 00:00:00

abstract：:Hypoxic regions within the tumor form due to imbalances between cell proliferation and angiogenesis; specifically, temporary closure or a reduced flow due to abnormal vasculature. They create environments where cancer cells acquire resistance to therapies. Therefore, the development of therapeutic approaches targeting...

journal_title：Molecular therapy. Methods & clinical development

authors： Kagiya G,Ogawa R,Hyodo F,Yamashita K,Nakamura M,Ishii A,Sejimo Y,Tominaga S,Murata M,Tanaka Y,Hatashita M

更新日期：2016-03-02 00:00:00

abstract：:Hypophosphatasia (HPP) is an inherited disease caused by genetic mutations in the gene encoding tissue-nonspecific alkaline phosphatase (TNALP). This results in defects in bone and tooth mineralization. We recently demonstrated that TNALP-deficient (Akp2 (-/-) ) mice, which mimic the phenotype of the severe infantile ...

journal_title：Molecular therapy. Methods & clinical development

authors： Nakamura-Takahashi A,Miyake K,Watanabe A,Hirai Y,Iijima O,Miyake N,Adachi K,Nitahara-Kasahara Y,Kinoshita H,Noguchi T,Abe S,Narisawa S,Millán JL,Shimada T,Okada T

更新日期：2016-02-03 00:00:00

abstract：:Duchenne muscular dystrophy (DMD) is a fatal disease of striated muscle deterioration. A unique therapeutic approach for DMD is the use of synthetic membrane stabilizers to protect the fragile dystrophic sarcolemma against contraction-induced mechanical stress. Block copolymer-based membrane stabilizer poloxamer 188 (...

journal_title：Molecular therapy. Methods & clinical development

authors： Houang EM,Haman KJ,Filareto A,Perlingeiro RC,Bates FS,Lowe DA,Metzger JM

更新日期：2015-11-11 00:00:00

abstract：:Gene transfer to hematopoietic stem cells with integrating vectors not only allows sustained correction of monogenic diseases but also tracking of individual clones in vivo. Quantitative real-time PCR (qPCR) has been shown to be an accurate method to quantify individual stem cell clones, yet due to frequently limited ...

journal_title：Molecular therapy. Methods & clinical development

authors： Giordano FA,Appelt JU,Link B,Gerdes S,Lehrer C,Scholz S,Paruzynski A,Roeder I,Wenz F,Glimm H,von Kalle C,Grez M,Schmidt M,Laufs S

更新日期：2015-04-01 00:00:00

abstract：:Recombinant adeno-associated virus (rAAV) is currently the best vector for gene delivery into the skeletal muscle. However, the 5-kb packaging size of this virus is a major obstacle for large gene transfer. This past decade, many different strategies were developed to circumvent this issue (concatemerization-splicing,...

journal_title：Molecular therapy. Methods & clinical development

authors： Pryadkina M,Lostal W,Bourg N,Charton K,Roudaut C,Hirsch ML,Richard I

更新日期：2015-03-25 00:00:00

abstract：:Insertional mutagenesis has been associated with malignant cell transformation in gene therapy protocols, leading to discussions about vector security. Therefore, clonal analysis is important for the assessment of vector safety and its impact on patient health. Here, we report a unique approach to assess dynamic chang...

journal_title：Molecular therapy. Methods & clinical development

authors： Zanatta DB,Tsujita M,Borelli P,Aguiar RB,Ferrari DG,Strauss BE

更新日期：2014-11-19 00:00:00

abstract：:Hemophilia A, caused by a deficiency in factor VIII (FVIII), is the most severe inherited bleeding disorder. Hemophilia A is an attractive gene therapy candidate because even small increases in FVIII levels will positively alter the phenotype. While several vectors are under investigation, gene addition from an integr...

journal_title：Molecular therapy. Methods & clinical development

authors： Staber JM,Pollpeter MJ,Arensdorf A,Sinn PL,Rutkowski DT,McCray PB Jr

更新日期：2014-09-10 00:00:00

abstract：:Preventing untoward immune responses against a specific antigen is a major challenge in different clinical settings such as gene therapy, transplantation, or autoimmunity. Following intramuscular delivery of recombinant adeno-associated virus (rAAV)-derived vectors, transgene rejection can be a roadblock to successful...

journal_title：Molecular therapy. Methods & clinical development

authors： Moreau A,Vandamme C,Segovia M,Devaux M,Guilbaud M,Tilly G,Jaulin N,Le Duff J,Cherel Y,Deschamps JY,Anegon I,Moullier P,Cuturi MC,Adjali O

更新日期：2014-07-23 00:00:00

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

authors： Yoon SY,Gay-Antaki C,Ponde DE,Poptani H,Vite CH,Wolfe JH

更新日期：2014-06-04 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

authors： Sack BK,Herzog RW,Terhorst C,Markusic DM

更新日期：2014-04-30 00:00:00

abstract：:Possible risks and lack of donor livers limit application of liver transplantation. Liver cell transplantation is, at this moment, not a feasible alternative because engraftment in the liver is poor. Furthermore, there is also shortage of cells suitable for transplantation. Fetal liver cells are able to proliferate in...

journal_title：Molecular therapy. Methods & clinical development

authors： El Filali E,Duijst S,Hiralall JK,Legrand N,van Gulik T,Hoekstra R,Seppen J

更新日期：2014-03-12 00:00:00