abstract：:Surfactant protein B (SPB) deficiency is a severe monogenic interstitial lung disorder that leads to loss of life in infants as a result of alveolar collapse and respiratory distress syndrome. The development and assessment of curative therapies for the deficiency are limited by the general lack of well-characterized ...

journal_title：Molecular therapy. Methods & clinical development

authors： Munis AM,Hyde SC,Gill DR

更新日期：2020-11-20 00:00:00

abstract：:Lentiviral vectors (LVs) are increasingly employed in gene and cell therapy. Standard laboratory production of LVs is not easily scalable, and research-grade LVs often contain contaminants that can interfere with downstream applications. Moreover, purified LV production pipelines have been developed mainly for costly,...

journal_title：Molecular therapy. Methods & clinical development

authors： Soldi M,Sergi Sergi L,Unali G,Kerzel T,Cuccovillo I,Capasso P,Annoni A,Biffi M,Rancoita PMV,Cantore A,Lombardo A,Naldini L,Squadrito ML,Kajaste-Rudnitski A

更新日期：2020-10-20 00:00:00

abstract：:Recombinant adeno-associated virus (rAAV) is one of the main vectors used in gene therapy. An accurate genome titer is not only critical for clinical dosing, but also a prerequisite for many analytical assays for AAV product characterization. AAV genome titer is traditionally determined by qPCR; however, assay precisi...

journal_title：Molecular therapy. Methods & clinical development

authors： Wang Y,Menon N,Shen S,Feschenko M,Bergelson S

更新日期：2020-10-01 00:00:00

abstract：:Human immunodeficiency virus (HIV) is an attractive target for chimeric antigen receptor (CAR) therapy. CAR T cells have proved remarkably potent in targeted killing of cancer cells, and we surmised that CAR T cells could prove useful in eradicating HIV-infected cells. Toward this goal, we interrogate several neutrali...

journal_title：Molecular therapy. Methods & clinical development

authors： Urak RZ,Soemardy C,Ray R,Li S,Shevchenko G,Scott T,Lim L,Wang X,Morris KV

更新日期：2020-09-28 00:00:00

abstract：:Identification and characterization of disease-associated variants in monogenic disorders is an important aspect of diagnosis, genetic counseling, prediction of disease severity, and development of therapy. However, the effects of disease-associated variants on pre-mRNA splicing and mRNA degradation are difficult to p...

journal_title：Molecular therapy. Methods & clinical development

authors： Broeders M,Smits K,Goynuk B,Oussoren E,van den Hout HJMP,Bergsma AJ,van der Ploeg AT,Pijnappel WWMP

更新日期：2020-09-16 00:00:00

abstract：:Transforming growth factor β (TGF-β)/Smad3 signaling plays a central role in chronic heart disease. Here, we report that targeting Smad3 with a Smad3 inhibitor SIS3 in an established mouse model of hypertension significantly improved cardiac dysfunctions by preserving the left ventricle (LV) ejection fraction (LVEF) a...

journal_title：Molecular therapy. Methods & clinical development

authors： Meng J,Qin Y,Chen J,Wei L,Huang XR,Yu X,Lan HY

更新日期：2020-08-05 00:00:00

abstract：:Extracellular vesicles (EVs) are membranous structures that protect RNAs from damage when circulating in complex biological fluids, such as plasma. RNAs are extremely specific to health and disease, being powerful tools for diagnosis, treatment response monitoring, and development of new therapeutic strategies for sev...

journal_title：Molecular therapy. Methods & clinical development

authors： Gaspar LS,Santana MM,Henriques C,Pinto MM,Ribeiro-Rodrigues TM,Girão H,Nobre RJ,Pereira de Almeida L

更新日期：2020-07-15 00:00:00

abstract：:We present an overview of clinical trials involving gene editing using clustered interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9), transcription activator-like effector nucleases (TALENs), or zinc finger nucleases (ZFNs) and discuss the underlying mechanisms. In cancer immunotherapy, g...

journal_title：Molecular therapy. Methods & clinical development

authors： Ernst MPT,Broeders M,Herrero-Hernandez P,Oussoren E,van der Ploeg AT,Pijnappel WWMP

更新日期：2020-07-03 00:00:00

abstract：:Methods for customizing and improving virus vector tropism are limited. In this study, we introduce a microRNA (miRNA)-regulated molecular method to enhance vector transduction without genome alteration. Based on the importance of adenovirus (Ad) vectors for cancer and gene treatment, we exemplified this technology fo...

journal_title：Molecular therapy. Methods & clinical development

authors： Gao J,Zhang W,Mese K,Bunz O,Lu F,Ehrhardt A

更新日期：2020-06-18 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

authors： Zou C,Vercauteren KOA,Michailidis E,Kabbani M,Zoluthkin I,Quirk C,Chiriboga L,Yazicioglu M,Anguela XM,Meuleman P,High KA,Herzog RW,de Jong YP

更新日期：2020-06-02 00:00:00

abstract：:There is no effective serologic parameter to distinguish different types of pancreatitis now. To distinguish between acute pancreatitis (AP) and acute exacerbations of chronic pancreatitis (CP) and to determine whether fibrosis occurs in CP, we evaluated the ability to produce white blood cells (WBCs), the neutrophil-...

journal_title：Molecular therapy. Methods & clinical development

authors： Luo L,Zhang J,Yang J,Zhang H,Tang Y,Yang D,Dong H,Wu Y,Wang H,Ni B,Tian Z

更新日期：2020-05-22 00:00:00

abstract：:Herpes simplex keratitis (HSK) is the most common cause of corneal blindness in developed nations, caused by primary or recurrent herpes simplex virus 1 (HSV-1) infection of the cornea. Latent infection of HSV-1, especially in the trigeminal ganglion (TG), causes recurrence of HSV-1 infection. As antiviral treatment i...

journal_title：Molecular therapy. Methods & clinical development

authors： Chen Y,Zhi S,Liang P,Zheng Q,Liu M,Zhao Q,Ren J,Cui J,Huang J,Liu Y,Songyang Z

更新日期：2020-05-22 00:00:00

abstract：:Pompe disease is an autosomal recessive lysosomal storage disorder characterized by progressive muscle weakness. The disease is caused by mutations in the acid α-glucosidase (GAA) gene. Despite the currently available enzyme replacement therapy (ERT), roughly half of the infants with Pompe disease die before the age o...

journal_title：Molecular therapy. Methods & clinical development

authors： Stok M,de Boer H,Huston MW,Jacobs EH,Roovers O,Visser TP,Jahr H,Duncker DJ,van Deel ED,Reuser AJJ,van Til NP,Wagemaker G

更新日期：2020-05-04 00:00:00

abstract：:Preclinical studies have demonstrated that a single injection of an adeno-associated virus (AAV) vector into the cerebrospinal fluid (CSF) can achieve widespread gene transfer throughout the central nervous system. Successfully translating this approach to humans requires identifying factors that influence AAV distrib...

journal_title：Molecular therapy. Methods & clinical development

authors： Hinderer C,Katz N,Dyer C,Goode T,Johansson J,Bell P,Richman L,Buza E,Wilson JM

更新日期：2020-04-18 00:00:00

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 requi...

journal_title：Molecular therapy. Methods & clinical development

authors： Jasperse B,O'Connell CM,Wang Y,Verardi PH

更新日期：2020-03-30 00:00:00

abstract：:Adoptive natural killer (NK) cell therapy is attaining promising clinical outcomes in recent years, but improvements are needed. Genetic modification of NK cells with a tumor antigen-specific receptor on their surface coupled to intracellular signaling domains may lead to enhanced cytotoxicity against malignant cells....

journal_title：Molecular therapy. Methods & clinical development

authors： Gong Y,Klein Wolterink RGJ,Janssen I,Groot AJ,Bos GMJ,Germeraad WTV

更新日期：2020-03-29 00:00:00

abstract：:The delivery of factor VIII (FVIII) through gene and/or cellular platforms has emerged as a promising hemophilia A treatment. Herein, we investigated the suitability of human placental cells (PLCs) as delivery vehicles for FVIII and determined an optimal FVIII transgene to produce/secrete therapeutic FVIII levels from...

journal_title：Molecular therapy. Methods & clinical development

authors： El-Akabawy N,Rodriguez M,Ramamurthy R,Rabah A,Trevisan B,Morsi A,George S,Shields J,Meares D,Farland A,Atala A,Doering CB,Spencer HT,Porada CD,Almeida-Porada G

更新日期：2020-03-14 00:00:00

abstract：:Type 1 diabetes affects 20 million patients worldwide. Insulin is the primary and commonly the sole therapy for type 1 diabetes. However, only a minority of patients attain the targeted glucose control and reduced adverse events. We tested urocortin 2 gene transfer as single-agent therapy for insulin deficiency using ...

journal_title：Molecular therapy. Methods & clinical development

authors： Gao MH,Giamouridis D,Lai NC,Guo T,Xia B,Kim YC,Huu VAN,Skowronska-Krawczyk D,Lantier L,Bhargava R,Hammond HK

更新日期：2019-12-14 00:00:00

abstract：:The His723Arg (H723R) mutation in SLC26A4, encoding pendrin, is the most prevalent mutation in East Asia, resulting in DFNB4, an autosomal recessive type of genetic hearing loss. Although the main pathological mechanism of H723R was identified as a protein-folding defect in pendrin, there is still no curative treatmen...

journal_title：Molecular therapy. Methods & clinical development

authors： Choi HJ,Lee HJ,Choi JY,Jeon IH,Noh B,Devkota S,Lee HW,Eo SK,Choi JY,Lee MG,Jung J

更新日期：2019-11-30 00:00:00

abstract：:Because many peptide and peptide-mimetic drugs are substrates of peptide transporter 1, it is important to evaluate the peptide transporter 1-mediated intestinal absorption of drug candidates in the early phase of drug development. Although intestinal cell lines treated with inhibitors of peptide transporter 1 are wid...

journal_title：Molecular therapy. Methods & clinical development

authors： Kawai K,Negoro R,Ichikawa M,Yamashita T,Deguchi S,Harada K,Hirata K,Takayama K,Mizuguchi H

更新日期：2019-11-21 00:00:00

abstract：:Gene transfer to and correction of hematopoietic stem cells (HSCs) are ideal strategies to cure a number of congenital and acquired disorders. However, transgene products may trigger immunological rejection of modified cells, limiting their therapeutic benefits. Preclinical and clinical data indicate that myeloablativ...

journal_title：Molecular therapy. Methods & clinical development

authors： Drysdale CM,Tisdale JF,Uchida N

更新日期：2019-10-31 00:00:00

abstract：:rAAVrh74.MCK.GALGT2 is a surrogate gene therapy that inhibits muscular dystrophy in multiple animal models. Here, we report on a dose-response study of functional muscle GALGT2 expression as well as toxicity and biodistribution studies after systemic intravenous (i.v.) delivery of rAAVrh74.MCK.GALGT2. A dose of 4.3 × ...

journal_title：Molecular therapy. Methods & clinical development

authors： Zygmunt DA,Xu R,Jia Y,Ashbrook A,Menke C,Shao G,Yoon JH,Hamilton S,Pisharath H,Bolon B,Martin PT

更新日期：2019-10-21 00:00:00

abstract：:Gene therapy has been suggested as a plausible novel approach to achieve seizure control in patients with focal epilepsy that do not adequately respond to pharmacological treatment. We investigated the seizure-suppressant potential of combinatorial neuropeptide Y and Y2 receptor single vector gene therapy based on ade...

journal_title：Molecular therapy. Methods & clinical development

authors： Melin E,Nanobashvili A,Avdic U,Gøtzsche CR,Andersson M,Woldbye DPD,Kokaia M

更新日期：2019-09-18 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

authors： Shin HS,Jung SB,Park S,Dua P,Lee DK

更新日期：2019-09-12 00:00:00

abstract：:Endotoxin is the most common contaminant found in protein samples. Even a small amount of endotoxin can induce strong allergic reaction and death of a host organism. Endotoxin is also often detected in recombinant adeno-associated virus (rAAV) stocks prepared in research laboratories using off-the-shelf reagents; puri...

journal_title：Molecular therapy. Methods & clinical development

authors： Kondratova L,Kondratov O,Ragheb R,Zolotukhin S

更新日期：2019-09-06 00:00:00

abstract：:The overall goal of our research is to establish a preformed molecular guidance pathway to direct the growth of dopaminergic axons from embryonic ventral mesencephalon (VM), tissue placed within the substantia nigra (SN), into the striatum to reconstruct the nigrostriatal pathway in a hemi-Parkinson's disease rat mode...

journal_title：Molecular therapy. Methods & clinical development

authors： Ghosh B,Zhang C,Ziemba KS,Fletcher AM,Yurek DM,Smith GM

更新日期：2019-07-11 00:00:00

abstract：:Adeno-associated viruses (AAVs) are the vector of choice for gene therapy in the eye, and self-complementary AAVs (scAAVs), which do not require second-strand DNA synthesis, can be transduced into cells of the trabecular meshwork (TM). The scAAV transduction patterns in the anterior segment of normotensive eyes have b...

journal_title：Molecular therapy. Methods & clinical development

authors： Lee SH,Sim KS,Kim CY,Park TK

更新日期：2019-07-10 00:00:00

abstract：:Exudative age-related macular degeneration (AMD), characterized by choroidal neovascularization (CNV), is the leading cause of irreversible blindness in developed countries. Anti-vascular endothelial growth factor (VEGF) drugs are the standard treatment for AMD, but they have limitations. Cell therapy is a promising a...

journal_title：Molecular therapy. Methods & clinical development

authors： Cao J,Yang R,Smith TE,Evans S,McCollum GW,Pomerantz SC,Petley T,Harris IR,Penn JS

更新日期：2019-05-22 00:00:00

abstract：:Validation of gene transfer vectors containing tissue-specific promoters in cell-based functional assays poses a formidable challenge for gene therapy product development. Here, we describe a novel approach based on CRISPR/dCas9 transcriptional activation to achieve robust transgene expression from transgene cassettes...

journal_title：Molecular therapy. Methods & clinical development

authors： McDougald DS,Duong TT,Palozola KC,Marsh A,Papp TE,Mills JA,Zhou S,Bennett J

更新日期：2019-03-28 00:00:00

abstract：:The tuberculosis (TB) vaccine MTBVAC is the only live-attenuated Mycobacterium tuberculosis (Mtb)-based vaccine in clinical development, and it confers superior protection in different animal models compared to the current vaccine, BCG (Mycobacterium bovis bacillus Calmette-Guérin). With the aim of using MTBVAC as a v...

journal_title：Molecular therapy. Methods & clinical development

authors： Broset E,Saubi N,Guitart N,Aguilo N,Uranga S,Kilpeläinen A,Eto Y,Hanke T,Gonzalo-Asensio J,Martín C,Joseph-Munné J

更新日期：2019-02-07 00:00:00

abstract：:Systemic delivery of adeno-associated viral (AAV) vectors has been evaluated for the treatment of several liver diseases, including homozygous familial hypercholesterolemia, ornithine transcarbamylase deficiency, and hemophilia. Here, we evaluated this approach for the treatment of Crigler-Najjar syndrome. We administ...

journal_title：Molecular therapy. Methods & clinical development

authors： Greig JA,Calcedo R,Kuri-Cervantes L,Nordin JML,Albrecht J,Bote E,Goode T,Chroscinski EA,Bell P,Richman LK,Betts MR,Wilson JM

更新日期：2018-12-05 00:00:00

abstract：:Adeno-associated virus (AAV) vectors have become one of the most widely used gene transfer tools in human gene therapy. Considerable effort is currently being focused on AAV capsid engineering strategies with the aim of developing novel variants with enhanced tropism for specific human cell types, decreased human sero...

journal_title：Molecular therapy. Methods & clinical development

authors： Cabanes-Creus M,Ginn SL,Amaya AK,Liao SHY,Westhaus A,Hallwirth CV,Wilmott P,Ward J,Dilworth KL,Santilli G,Rybicki A,Nakai H,Thrasher AJ,Filip AC,Alexander IE,Lisowski L

更新日期：2018-11-01 00:00:00

abstract：:Lentiviral vectors have emerged as an efficient, safe therapeutic tool for gene therapy based on hematopoietic stem cells (HSCs) or T cells. However, the monitoring of transduced cells in preclinical models remains challenging because of the inefficient transduction of murine primary T cells with lentiviral vectors, i...

journal_title：Molecular therapy. Methods & clinical development

authors： Delville M,Soheili T,Bellier F,Durand A,Denis A,Lagresle-Peyrou C,Cavazzana M,Andre-Schmutz I,Six E

更新日期：2018-08-08 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

authors： Clarke D,Pearse Y,Kan SH,Le SQ,Sanghez V,Cooper JD,Dickson PI,Iacovino M

更新日期：2018-07-23 00:00:00

abstract：:Liver metabolism disorders are attractive targets for gene therapy, because low vector doses can reverse the buildup of toxic metabolites in the blood. Crigler-Najjar syndrome is an inherited disorder of bilirubin metabolism that is caused by the absence of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) act...

journal_title：Molecular therapy. Methods & clinical development

authors： Greig JA,Nordin JML,Draper C,McMenamin D,Chroscinski EA,Bell P,Gray JT,Richman LK,Wilson JM

更新日期：2018-07-21 00:00:00

abstract：:Recombinant adeno-associated virus (rAAV)rh74.MCK.GALGT2 is a muscle-specific gene therapy that is being developed to treat forms of muscular dystrophy. Here we report on an isolated limb infusion technique in a non-human primate model, where hindlimb blood flow is transiently isolated using balloon catheters to conce...

journal_title：Molecular therapy. Methods & clinical development

authors： Xu R,Jia Y,Zygmunt DA,Cramer ML,Crowe KE,Shao G,Maki AE,Guggenheim HN,Hood BC,Griffin DA,Peterson E,Bolon B,Cheatham JP,Cheatham SL,Flanigan KM,Rodino-Klapac LR,Chicoine LG,Martin PT

更新日期：2018-07-14 00:00:00

abstract：:Recombinant adeno-associated virus (rAAV) vectors are considered ideal vehicles for human gene therapy. Meanwhile, non-viral strategies, such as transfection agents (TAs), have also shown promise to deliver genetic materials, such as siRNA. Transduction with the rAAV vector is performed concurrently with transfection ...

journal_title：Molecular therapy. Methods & clinical development

authors： Guo P,Yu C,Wang Q,Zhang R,Meng X,Feng Y

更新日期：2018-04-12 00:00:00

abstract：:X-linked severe combined immunodeficiency (SCID-X1) is caused by mutations in the interleukin-2 receptor γ chain gene (IL2RG), and it is characterized by profound defects in T, B, and natural killer (NK) cell functions. Transplantation of hematopoietic stem/progenitor cells (HSPCs) genetically corrected with early mur...

journal_title：Molecular therapy. Methods & clinical development

authors： Poletti V,Charrier S,Corre G,Gjata B,Vignaud A,Zhang F,Rothe M,Schambach A,Gaspar HB,Thrasher AJ,Mavilio F

更新日期：2018-03-10 00:00:00

abstract：:Gene therapy has been shown to be a feasible approach to treat inherited disorders in vivo. Among the currently used viral vector systems, adeno-associated virus (AAV) vectors are the most advanced and have been applied in patients successfully. An important drawback of non-integrating AAV vectors is their loss of exp...

journal_title：Molecular therapy. Methods & clinical development

authors： Shi X,Ykema MR,Hazenoot J,Ten Bloemendaal L,Mancini I,Odijk M,de Haan P,Bosma PJ

更新日期：2018-02-27 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

authors： Alrafiah A,Karyka E,Coldicott I,Iremonger K,Lewis KE,Ning K,Azzouz M

更新日期：2018-01-31 00:00:00