Journal of gene therapy最新文献

{"title":"RPE65 Variation RPE65 pG140E, c419G>A, First case presentation","authors":"","doi":"10.13188/2381-3326.1000008","DOIUrl":"https://doi.org/10.13188/2381-3326.1000008","url":null,"abstract":"We are reporting a new variation RPE65 pG140E, c419G>A. An asymptomatic male with fine bright white dotes in macula and generalized constricted visual fields. Introduction The RPE65 protein is the source of isomerohrydrolase activity (conversion of all-trans retinyl ester to 11-cis retinol) in the retinal pigment epithelium [1]. The characterization of RPE65 gene was first described by Nicoletti et al. 1995 [2], which encodes the abundant 61-kD protein in Retinal Pigment Epithelium (RPE) monolayer simple epithelium opposed to the outer surface of the retina photoreceptor cells. RPE works in metabolism in outer layers that are essential to continued maintenance of the photoreceptor cells, including vision functionality as visual cycle photoreceptor recycling and outer segment phagocitosis [3]. The gene is maps to human chromosome 1p31. Among functions are 1) Phagocytizes periodically the tips of outer segments, process whose defects leads to retinal degeneration, 2) RPE65 is site of many enzymes involved in retinoid metabolism, including retinyl ester synthetase and 3) Lecithin: retinol acyltranferase, 4) Retinyl ester hydrolase, 5) Retinol isomerase, 6) 11-cis retinol deshidrogenase as well as 7) Rpe-/retina-specific cellular retinaldehyde binding protein, 8) ion transport 9) digestion of phagosomes and 10) detoxification of photoreceptors by products. Autosomal recessive childhood-onset severe retinal dystrophy (arCSRD) designates a heterogenous group of disorders affecting rod and cone photoreceptors simultaneously [4]. Disease genes implicated in other forms of arCSRD are expected to encode proteins presents in the neuroretina, it is in intimate contact with the outer segments of rods and cones via the microvillus surrounding the photoreceptos. The first family described with RPE65 mutation was in 1963 was by Waardenburg all normal children from two affected parents were reported [5]. Chung and Talboulsi in 2009 described another family with moderate impairment at infancy that progresses to total blindness by mild to late adulthood [6]. Morimura in 1998 summarized the clinical criteria distinguishing retinitis pigmentosa (RP) from LCA, however variability is among them [7]. We are reporting a new variation RPE65 pG140E, c419G>A (new variation, not previously reported from father) and p. I98HfsX26, c.292_311del20 (known pathogenic variationfrom mother) in a 3 years old. Methodology We examined a 3 years old that starts bumping into objects since 1 year old. Mother noticed he likes to stared at sun. He is scared at walking and eating and mother alleged he looks not secure. During ocular examination he presented with Central Steady and Maintains vision OU, no Nystagmus. Fundus examination is about normal, central choroidal shown no thickenings of vessels, there are scarce fine dots all over the macula (Figure 1), the diagnosis is inherited retina dystrophy OU. We then perform ocular full examination to parents and sibling and we establish a more ","PeriodicalId":90218,"journal":{"name":"Journal of gene therapy","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73224479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Oncolytic Herpes Simplex Virus Design based on the Common Overexpression of microRNA-21 in Tumors.","authors":"M Marzulli,&nbsp;L Mazzacurati,&nbsp;M Zhang,&nbsp;W F Goins,&nbsp;M E Hatley,&nbsp;J C Glorioso,&nbsp;J B Cohen","doi":"10.13188/2381-3326.1000007","DOIUrl":"https://doi.org/10.13188/2381-3326.1000007","url":null,"abstract":"<p><strong>Background: </strong>Recognition sequences for microRNAs (miRs) that are down-regulated in tumor cells have recently been used to render lytic viruses tumor-specific. Since different tumor types down-regulate different miRs, this strategy requires virus customization to the target tumor. We have explored a feature that is shared by many tumor types, the up-regulation of miR-21, as a means to generate an oncolytic herpes simplex virus (HSV) that is applicable to a broad range of cancers.</p><p><strong>Methods: </strong>We assembled an expression construct for a dominant-negative (dn) form of the essential HSV replication factor U_L9 and inserted tandem copies of the miR-21 recognition sequence (T21) in the 3' untranslated region. Bacterial Artificial Chromosome (BAC) recombineering was used to introduce the dnU_L9 construct with or without T21 into the HSV genome. Virus was produced by transfection and replication was assessed in different tumor and control cell lines.</p><p><strong>Results: </strong>Virus production was conditional on the presence of the T21 sequence. The dnU_L9-T21 virus replicated efficiently in tumor cell lines, less efficiently in cells that contained reduced miR-21 activity, and not at all in the absence of miR-21.</p><p><strong>Conclusion: </strong>miR-21-sensitive expression of a dominant-negative inhibitor of HSV replication allows preferential destruction of tumor cells in vitro. This observation provides a basis for further development of a widely applicable oncolytic HSV.</p>","PeriodicalId":90218,"journal":{"name":"Journal of gene therapy","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6241327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36706316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-124 suppresses tumor cell proliferation and invasion by targeting CD164 signaling pathway in non-small cell lung cancer.","authors":"Jing Lin,&nbsp;Kai Xu,&nbsp;Jun Wei,&nbsp;Amy B Heimberger,&nbsp;Jack A Roth,&nbsp;Lin Ji","doi":"10.13188/2381-3326.1000006","DOIUrl":"https://doi.org/10.13188/2381-3326.1000006","url":null,"abstract":"<p><p>MicroRNAs play critical roles in regulating gene expression and various cellular processes in human cancer malignant progression. Down-regulated expression of miR-124 gene has been shown to be significantly associated with a poor prognosis in patients with non-small cell lung cancer (NSCLC) but its biological function and regulatory roles in lung cancer tumorigenesis are largely unknown. In this study, we aimed to determine effects of ectopic expression of miR-124 on tumor cell proliferation, invasion, and induction of apoptosis by DOTAP:Cholesterol nanoparticle-mediated gene transfer and identify its endogenous targets under physiological conditions in NSCLC cells. Overexpression of miR-124 significantly suppresses tumor cell proliferation, colony formation, migration, and induction of apoptosis in H322 and A549 cells. Two endogenous miR-124 targeting sites in the 3'UTR of CD164 mRNA are identified by a stem-loop-array reverse transcription PCR (SLA-RT-PCR) assay in H1299 cells under physiological condition. Ectopic expression of miR-124 induces CD164 mRNA cleavage and down-regulated its gene and protein expression. Our results suggest that miR-124 function as a tumor suppressor miRNA and suppress tumor proliferation and aggression by directly targeting oncogenic CD164 signaling pathway in NSCLC.</p>","PeriodicalId":90218,"journal":{"name":"Journal of gene therapy","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927004/pdf/nihms763264.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34700415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Incretin Effects of Exendin-4 Expressing Chimeric Plasmid Based On Two-Step Transcription Amplification System with Dendritic Bioreducible Polymer for the Treatment of Type 2 Diabetes.","authors":"Pyung-Hwan Kim,&nbsp;Minhyung Lee,&nbsp;Kihoon Nam,&nbsp;Sung Wan Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Glucagon-like peptide 1 (GLP-1) agonist, exenxdin-4, is currently being advanced as a promising diabetes remedy via a variety of incretin actions similar with GLP-1. In this study, we investigated an effective anti-diabetic therapy via exendin-4 expressing chimeric plasmid based on two-step transcription amplification (TSTA) system with dendrimer-type bioreducible polymer for more improved incretin-based gene therapy. Arginine-grafted poly (cystaminebisacrylamide-diaminohexane) (ABP)-conjugated poly (amido amine) (PAMAM) dendrimer (PAM-ABP) was used as gene carrier. PAM-ABP/chimeric DNA polyplex was markedly elevated exendin-4 expression in ectopic cells as well as increased insulin production through an enhanced activation of protein kinase K (PKA) induced by up-regulation of exendin-4-stimulated cyclic adenosine monophosphate (cAMP) in pancreatic β-cell. Consistent with these results, intravenous administration of PAM-ABP/chimeric DNA polyplex improved glucoregulotory effects, as well as increased insulin secretion by high expression of exendin-4 in blood in type 2 diabetic mice with no any toxicity. Our exendin-4 system can be attributed to provide a potential diabetes therapeutic agent for improved incretin gene therapy.</p>","PeriodicalId":90218,"journal":{"name":"Journal of gene therapy","volume":"1 1","pages":"7-15"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020291/pdf/nihms555045.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32352248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Incretin Effects of Exendin-4 Expressing Chimeric Plasmid Based On Two-Step Transcription Amplification System with Dendritic Bioreducible Polymer for the Treatment of Type 2 Diabetes.","authors":"Pyung-Hwan Kim, Minhyung Lee, K. Nam, S. W. Kim","doi":"10.13188/2381-3326.1000002","DOIUrl":"https://doi.org/10.13188/2381-3326.1000002","url":null,"abstract":"Glucagon-like peptide 1 (GLP-1) agonist, exenxdin-4, is currently being advanced as a promising diabetes remedy via a variety of incretin actions similar with GLP-1. In this study, we investigated an effective anti-diabetic therapy via exendin-4 expressing chimeric plasmid based on two-step transcription amplification (TSTA) system with dendrimer-type bioreducible polymer for more improved incretin-based gene therapy. Arginine-grafted poly (cystaminebisacrylamide-diaminohexane) (ABP)-conjugated poly (amido amine) (PAMAM) dendrimer (PAM-ABP) was used as gene carrier. PAM-ABP/chimeric DNA polyplex was markedly elevated exendin-4 expression in ectopic cells as well as increased insulin production through an enhanced activation of protein kinase K (PKA) induced by up-regulation of exendin-4-stimulated cyclic adenosine monophosphate (cAMP) in pancreatic β-cell. Consistent with these results, intravenous administration of PAM-ABP/chimeric DNA polyplex improved glucoregulotory effects, as well as increased insulin secretion by high expression of exendin-4 in blood in type 2 diabetic mice with no any toxicity. Our exendin-4 system can be attributed to provide a potential diabetes therapeutic agent for improved incretin gene therapy.","PeriodicalId":90218,"journal":{"name":"Journal of gene therapy","volume":"17 1","pages":"7-15"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90408729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}