Human Gene Therapy. Clinical Development

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Adeno-associated virus (AAV) vectors have become an important tool for delivering therapeutic genes for a wide range of neurological diseases. AAV serotypes possess differential cellular tropism in the central nervous system. Although several AAV serotypes or mutants have been reported to transduce the brain efficiently, conflicting data occurs across studies with the use of various rodent strains from different genetic backgrounds. Herein, we performed a systematic comparison of brain transduction properties among five AAV serotypes (AAV2, 5, 7, 8, and 9) in two common rodent strains (C57BL/6J and FVB/N), following local intra-striatal injection of AAV vectors encoding EGFP driven by the CBh promoter...

MiR-203 is known to target estrogen receptor α (ERα) in various cancer cell lines, such as MCF-7. However, whether miR-203 regulates ERα and contributes to the onset and progression of osteoarthritis (OA) is poorly understood. A combined protocol of the bilateral ovariectomy and the intra-articular monosodium iodoacetate (MIA) injection was applied to establish a postmenopausal OA model in rats. Real-time quantitative PCR was used to detect miR-203 and mRNAs and Western blotting was exploited to quantify the expressions on the protein level...

Cardiac hypertrophy is an adaptive cardiac response to heart stress. Sustained cardiac hypertrophy indicates higher risk of heart failure. Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been proved to be a key regulator of cardiac hypertrophy, but its mechanism remains largely unknown. Our study proposed to explore the regulatory mechanism of CaMKII in cardiac hypertrophy. We validated that CaMKII was upregulated in cardiac hypertrophy models in vivo and in vitro, and that knockdown of CaMKII attenuated Ang II-induced cardiac hypertrophy in vitro...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Background Hepatocellular carcinoma (HCC) is a most common malignancy in liver and is one of the leading causes of cancer-induced deaths over the world. Circular RNAs (circRNAs) have been proven to be related to cancer initiation and progression in mounting reports. However, research on the role of circRNAs in human cancers, including HCC, is still in its infancy. CircVAPA has been unmasked as oncogenic in colorectal cancer. Yet the function of circVAPA in HCC has never been elucidated. Materials and Methods CircVAPA, miR-377-3p and PSAP mRNA expression levels were detected by RT-qPCR...

The purpose of this study was to investigate the expression level of microRNA-4513 (miR-4513) in gastric cancer, and the underlying mechanisms of miR-4513 in regulating gastric cancer (GC) progression. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to measure the expression level of miR-4513 in GC cells. Transfection efficacy of synthetic miRNAs was examined by qRT-PCR. After synthetic miRNAs transfection, cell counting kit-8 assay and transwell invasion assay was conducted to measure biological changes in these groups...

Editor's note: Sir Patrick Vallance is Government Chief Scientific Adviser in the United Kingdom. Here he discusses his path from academia to industry to government, and he reflects on the crucial early conversations that were instrumental in positioning gene therapy research for successful clinical development.

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<i>In vivo</i> viral gene therapy and somatic cell therapy products (whether autologous, allogeneic or xenogeneic) that have been subjected to an <i>ex vivo</i> gene transfer procedure will normally be classified as genetically modified organisms (GMOs) in Europe, not just the gene transfer vectors used in their construction. These products are therefore expected to fulfil certain environmental requirements with regards to the biosafety aspects of their clinical use (which may be subject to review by government departments responsible for environmental affairs)...

microRNAs (miRNAs) have been widely recognized as crucial regulators for tumorigenesis. However, the role of miR-632 in hepatocellular carcinoma (HCC) remains largely unknown. miR-632 expression in HCC cell lines was determined by quantitative real-time PCR. The role of miR-632 expression on overall survival of HCC patients was examined at KM plotter website. The dual-luciferase reporter method was performed to investigate whether myc target 1 (MYCT1) was a target of miR-632. Cell counting kit-8 assay, colony formation assay, and transwell invasion assay were performed to examine cell proliferation, colony formation, and cell invasion of HCC cells...

Background The past 10 years witnessed a significant increase in the approval of cellular and gene therapy products worldwide. The US Food and Drug Administration (FDA) approved 3 gene therapy products within the last 4 months of 2017. The objective of this study was to examine the approval characteristics, discontinuations and cost of all cellular and gene therapy products approved worldwide. Data and Methods We conducted an electronic search of approved cell and gene therapy products from the databases of the main drug regulatory agencies including the US Food and Drug Administration, the European Medicines Agency (EMA), the Korea Ministry of Food and Drug Safety (MFDS), and Japan's Pharmaceuticals and Medical Devices Agency, China Food and Drug Administration, Ministry of Health and Social Development-Russia, Health Canada, and the Food and Drug Administration of the Philippines...

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor with high morbidity and mortality across the world. Recent findings have suggested that lncRNA HOXA-AS3 plays an important role in tumorigenesis and metastasis in a variety of cancers. However, the role of lncRNA HOXA-AS3 in the initiation and progression of HCC remains largely unclear. In the present study, HOXA-AS3 was highly expressed in HCC tumor tissues and cell lines. High HOXA-AS3 expression was correlated with low survival of HCC patients...

The purpose of this study was to examine the toxicity and side effects of a recombinant AAV8 vector, aimed to treat CNGA3-linked achromatopsia, after a single subretinal administration in cynomolgus macaques. Animals were followed in two studies: a 13-week study with 22 animals and a 28-day study with 12 animals. Both groups were divided into subgroups receiving either vehicle only, a low (1x1011 vector genomes (vg)), or a high dose (1x1012 vg) of rAAV.hCNGA3. In the 13-week study, an extra group received single high dose intravitreal injections...

General safety and toxicology assessments supporting in vivo lentiviral vector-based therapeutic development is sparse. We have previously demonstrated the efficacy of a lentiviral vector expressing fumarylacetoacetate hydrolase (LV-FAH) to cure animal models of hereditary tyrosinemia type 1. Therefore, we performed a complete preclinical toxicological evaluation of LV-FAH, in a large cohort (n = 20/group) of wildtype mice, and included matched groups of DEN/CCl4-induced liver injury mice to assess specific toxicity in fibrotic liver tissue...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.