Advances in cell and gene therapy最新文献

{"title":"Serpin B9-Insensitive Granzyme B Mutant Delivered by Engineered Capsid AAV Vectors Demonstrates Selective Killing of EGFR-Positive Cancer Cells","authors":"Dennis Makafui Dogbey,&nbsp;Krupa Naran,&nbsp;Stefan Barth","doi":"10.1155/acg2/8881294","DOIUrl":"https://doi.org/10.1155/acg2/8881294","url":null,"abstract":"<p>Cellular immunotherapy strategies that harness the cytotoxic properties of T and NK cells by releasing granzyme B have emerged as a crucial approach in cancer therapy for both hematological and solid tumors. However, the effective release and antitumor activities of granzyme B are significantly influenced by protease inhibitors including serpin B9. Gene delivery mechanisms that can counteract these limitations of cell-based immunotherapies are highly desired. In this regard, genetic modification of adeno-associated virus (AAV) capsids as vehicles for targeted delivery of therapeutic genes is an emerging area of research in the field of gene therapy of both monogenic and polygenic diseases. The insertion of antigen-specific antibody fragments and peptides into capsid sequences has been shown to redirect capsid tropism from native antigens to specific targets. Herein, we report on genetically engineered AAV2 capsid modified by inserting two antibody fragments: single-chain variable and single-domain antibodies and GE11 peptide, all specific for targeting epidermal growth factor receptor, at the N terminus of VP2. We observed an inverse correlation between the size of the inserted anti-EGFR moiety, capsid structure conservation, and vector yield. After demonstrating the proof of concept by confirming antigen-dependent transduction of cancer cells using AAV-GFP vectors, we further demonstrated that targeted AAV vectors encoding a protease-insensitive granzyme B mutant DNA cargo selectively eliminated cancer cells expressing serpin B9 in comparison to vectors encoding wild-type granzyme B in vitro. Our findings suggest that the challenges posed by intracellular expression of serpin B9 to antitumor T(NK) cell–dependent immunotherapies can be curtailed by utilizing the R201K granzyme mutant in immune-based therapy development.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/acg2/8881294","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273148","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":"Long-Term Correction of Murine Glycogen Storage Disease Type III by AAV-Mediated Gene Therapy Using an Immunotolerizing Dual Promoter to Express Bacterial Pullulanase","authors":"Kuo-An Liao,&nbsp;Jeong-A Lim,&nbsp;Su Jin Choi,&nbsp;Haiqing Yi,&nbsp;Baodong Sun","doi":"10.1155/acg2/4639392","DOIUrl":"https://doi.org/10.1155/acg2/4639392","url":null,"abstract":"<p><b>Background:</b> We recently reported an innovative gene therapy approach for GSD III using a recombinant adeno-associated virus serotype 9 vector (AAV9-Dual-Pull) expressing a bacterial debranching enzyme (pullulanase) driven by a tandem dual promoter that consists of an immunotolerizing liver-specific promoter (LSP) and the ubiquitous CMV enhance/chicken <i>β</i>-actin (CB) promoter. In this follow-up study, we evaluated the long-term efficacy of this gene therapy in GSD IIIa mice.</p><p><b>Methods:</b> Three-month-old GSD IIIa mice were intravenously injected with AAV9-LSP-Pull or AAV9-Dual-Pull at the same dose (2.5 × 10¹³ vg/kg). Tissues were collected after 9 months for AAV genome quantification, pullulanase expression determination, and glycogen content measurement. Liver and muscle enzymes in plasma and disease biomarker in urine were analyzed at multiple time points to examine the correction of liver and muscle damage. Behavioral tests were performed during the course of AAV treatment to evaluate the improvement of muscle function.</p><p><b>Results:</b> The AAV-Dual-Pull treatment led to persistent pullulanase expression and effective glycogen reduction in the liver, heart, and skeletal muscle, accompanied by the reversal of liver fibrosis, decrease of plasma enzyme activities, and long-term improvement of muscle function. The AAV-LSP-Pull treatment showed a better therapeutic efficacy in the liver but had no effect on the cardiac and skeletal muscles.</p><p><b>Conclusion:</b> Our results demonstrated the long-term efficacy and safety of systemic AAV9-Dual-Pull delivery in GSD IIIa mice. Future studies will test this gene therapy approach in GSD IIIa dogs prior to the clinical translation to GSD III patients.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/acg2/4639392","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840694","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":"The Impact of Niacin Administration on Plasma Lipids and Gene Expression in the Vervet Monkey Model (Chlorocebus aethiops)","authors":"Thobile Ngqaneka,&nbsp;Zandisiwe Emilia Magwebu,&nbsp;Kenechukwu Obikeze,&nbsp;Chesa Gift Chauke","doi":"10.1155/acg2/6679813","DOIUrl":"https://doi.org/10.1155/acg2/6679813","url":null,"abstract":"<p>Investigations conducted in mice and humans have reported that the nature and the amount of lipids in plasma can predict the likelihood of cardiovascular disease (CVD) development. Although niacin has a history as treatment for dyslipidemia, only a handful of clinical trials have investigated its efficiency in the prevention of the morbidity and mortality associated with CVDs. Therefore, the purpose of this study was to assess the impact of a niacin formulation on gene expression and plasma lipids using 16 vervet monkeys (8 controls and 8 experimental). The control group was given a maintenance diet only, while the experimental group’s diet was supplemented with niacin (100 mg/kg) for a period of 3 months, followed by 4-week washout. The investigated plasma lipids were total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. Gene expression of proprotein convertase subtilisin/kexin type 9 (<i>PCSK9</i>), cholesterol ester transfer protein (<i>CETP</i>), low-density lipoprotein receptor (<i>LDLR</i>), apolipoprotein B-100 (<i>APOB-100</i>) and sterol regulatory element–binding protein-2 (<i>SREBP-2</i>), which are involved in the reverse cholesterol transport (RCT) pathway, was also determined. Niacin administration resulted in statistically significant changes for total cholesterol and HDL-C, with the changes also significantly higher in females compared to males in the niacin-treated group. Furthermore, gene expression analysis revealed significant decrease in <i>CETP</i> during niacin treatment. The downregulation suggested that the vervet monkey model supports the HDL-C hypothesis. Future studies aimed at supporting these findings are directed towards exploring the epigenetic biomarkers influencing the RCT pathway to combat CVDs.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/acg2/6679813","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248711","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":"Silencing of B4Galnt1 Gene Prevents GM2 Accumulation in Tay-Sachs Cells","authors":"Nurselin Ateş,&nbsp;Orhan Kerim İnci,&nbsp;Seçil Akyıldız Demir,&nbsp;Volkan Seyrantepe","doi":"10.1155/2024/1099113","DOIUrl":"10.1155/2024/1099113","url":null,"abstract":"<p><i>Introduction</i>. The Tay-Sachs disease (TSD) is a progressive neurodegenerative disorder resulting from genetic mutations in the HEXA gene encoding the <i>α</i>-subunit of <i>β</i>-hexosaminidase A leading to the accumulation of GM2 ganglioside in the central nervous system. Multiple therapeutical strategies have been investigated such as gene therapy for Tay-Sachs patients; however, there is still no cure. In the present study, we suggest a new approach for the treatment of the Tay-Sachs disease with the concept of substrate reduction therapy by using AAV9-mediated RNAi technology targeting the <i>B4Galnt1</i> gene at the upstream of the enzymatic defect in TSD pathology to decrease GM2 biosynthesis and accumulation in cell models of TSD. <i>Material and Methods</i>. We employed AAV9-mediated shRNA transduction for mice and human Tay-Sachs cells. After transduction, expression levels of ganglioside metabolism genes were analyzed by RT-PCR and GM2 and lysosome-associated membrane protein 1 (LAMP1) protein levels were evaluated by immunocytochemistry analysis. <i>Results</i>. Here, we have shown that AAV9-shRNA transduction effectively reduced <i>B4Galnt1</i> expression in TSD cells demonstrating a reduction in GM2 accumulation and LAMP1. <i>Discussion</i>. Our data shows that AAV-mediated B4Galnt1-shRNA transduction can ameliorate disease pathologies by decreasing the lysosomal accumulation of GM2 through selectively reducing B4Gant1 activity in cell models of the Tay-Sachs disease. Therefore, we suggest promising novel experimental therapy for this devastating disease using a mouse model in the future.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"2024 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140378421","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":"Induction of Exocytosis Rescues Lysosomal GM2 Accumulation in Tay-Sachs Disease","authors":"Nurselin Ateş,&nbsp;Secil Akyildiz Demir,&nbsp;Volkan Seyrantepe","doi":"10.1155/2024/4047025","DOIUrl":"10.1155/2024/4047025","url":null,"abstract":"<p><i>Introduction</i>. The Tay-Sachs disease is a progressive neurodegenerative disorder that is caused by a genetic mutation in the HEXA gene coding the lysosomal <i>α</i>-subunit of <i>β</i>-hexosaminidase A. Currently, there is no effective treatment for Tay-Sachs. Induction of exocytosis as a potential treatment approach is suggested to restore lysosomal enlargement in several lysosomal storage diseases. Here, we aimed to test the therapeutic potential of two small molecules, <i>δ</i>-tocopherol and hydroxypropyl-<i>β</i>-cyclodextrin, in fibroblast and neuroglia cells derived from <i>Hexa-/-Neu3-/-</i> mice and Tay-Sachs patients. <i>Method</i>. The effect of two small molecules on lysosomal enlargement and GM2 accumulation in lysosomes was examined by LysoTracker staining and immunocytochemical colocalization analysis for GM2 and LAMP1. qRT-PCR and fluorometric enzyme assay were also used to investigate the effect of combined treatment on the level of neuraminidase 1, a negative regulator of exocytosis. <i>Results</i>. Single treatment with <i>δ</i>-tocopherol (5-40 <i>μ</i>M) and hydroxypropyl-<i>β</i>-cyclodextrin (10-50 <i>μ</i>M) for 48 hours led to significant induction of lysosomal exocytosis. We demonstrated that the combined treatment with <i>δ</i>-tocopherol (10 <i>μ</i>M) and hydroxypropyl-<i>β</i>-cyclodextrin (25 <i>μ</i>M) resulted in a significant reduction of lysosomal GM2 and downregulation of lysosomal Neu1 expression. <i>Conclusion</i>. In this study, we demonstrated that inducing exocytosis by <i>δ</i>-tocopherol and hydroxypropyl-<i>β</i>-cyclodextrin might have therapeutic potential to reduce GM2 storage and pathology in Tay-Sachs cells.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"2024 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140230266","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":"Comprehensive Comparison of AAV Purification Methods: Iodixanol Gradient Centrifugation vs. Immuno-Affinity Chromatography","authors":"Anh K. Lam,&nbsp;Patrick L. Mulcrone,&nbsp;Dylan Frabutt,&nbsp;Junping Zhang,&nbsp;Matthew Chrzanowski,&nbsp;Sreevani Arisa,&nbsp;Maite Munoz,&nbsp;Xin Li,&nbsp;Moanaro Biswas,&nbsp;David Markusic,&nbsp;Roland W. Herzog,&nbsp;Weidong Xiao","doi":"10.1155/2023/2339702","DOIUrl":"10.1155/2023/2339702","url":null,"abstract":"<div>\u0000 <p>Recombinant adeno-associated viruses (AAVs) have emerged as a widely used gene delivery platform for both basic research and human gene therapy. To ensure and improve the safety profile of AAV vectors, substantial efforts have been dedicated to the vector production process development using suspension HEK293 cells. Here, we studied and compared two downstream purification methods, iodixanol gradient ultracentrifugation versus immuno-affinity chromatography (POROS™ CaptureSelect™ AAVX column). We tested multiple vector batches that were separately produced (including AAV5, AAV8, and AAV9 serotypes). To account for batch-to-batch variability, each batch was halved for subsequent purification by either iodixanol gradient centrifugation or affinity chromatography. In parallel, purified vectors were characterized, and transduction was compared both <i>in vitro</i> and <i>in vivo</i> in mice (using multiple transgenes: Gaussia luciferase, eGFP, and human factor IX). Each purification method was found to have its own advantages and disadvantages regarding purity, viral genome (vg) recovery, and relative empty particle content. Differences in transduction efficiency were found to reflect batch-to-batch variability rather than disparities between the two purification methods, which were similarly capable of yielding potent AAV vectors.</p>\u0000 </div>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"2023 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10735247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138833260","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":"Therapeutic Effect of Hydrodynamics-Based Delivery of Matrix Metalloproteinase-13 Gene on Thioacetamide-Induced Liver Fibrosis in Rats","authors":"Takeshi Yokoo,&nbsp;Kenya Kamimura,&nbsp;Ryosuke Nozawa,&nbsp;Moeno Sugita,&nbsp;Osamu Shibata,&nbsp;Yuji Kobayashi,&nbsp;Hiroyuki Abe,&nbsp;Hiromi Miura,&nbsp;Masato Ohtsuka,&nbsp;Shuji Terai","doi":"10.1155/2023/8842424","DOIUrl":"10.1155/2023/8842424","url":null,"abstract":"<div>\u0000 <p>Liver cirrhosis is the final stage of chronic liver disease and can be life-threatening. Despite extensive studies on its treatment, a standard therapy is yet to be developed. Considering the complex mechanism of fibrogenic and fibrolytic processes in liver cirrhosis, combined therapy may have clinically significant effects on cirrhotic livers. In this study, we used thioacetamide (TAA) administration and <i>matrix metalloproteinase-13</i> (<i>MMP13</i>) gene delivery to induce extracellular matrix generation and degradation in rats. The aim of this study was to determine whether hydrodynamics-based gene delivery of <i>MMP13</i> to cirrhotic liver has regressive and suppressive effects on fibrogenesis. <i>MMP13</i>-encoding plasmids were hydrodynamically delivered to TAA-induced cirrhotic livers, and intravascular pressure was monitored. Therapeutic effect with and without continuous TAA exposure was assessed 8 weeks after the gene delivery. Test results indicated successful gene delivery and gene expression in the cirrhotic livers. Furthermore, microscopic imaging showed that <i>MMP13</i> delivery resulted in significant degradation of fibrotic areas. Quantitative analysis of hydroxyproline content supported the microscopic findings. These results suggest that transgene delivery of <i>MMP13</i> can be a promising candidate to treat liver fibrosis and that hydrodynamics-based gene delivery can be a good option for delivery of <i>MMP13</i> to cirrhotic livers.</p>\u0000 </div>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"2023 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2023/8842424","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136210894","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":"Intra-Articular AAV9 α-l-Iduronidase Gene Replacement in the Canine Model of Mucopolysaccharidosis Type I","authors":"Raymond Yu-Jeang Wang,&nbsp;Shih-Hsin Kan,&nbsp;Haoyue Zhang,&nbsp;Jodi D. Smith,&nbsp;Afshin Aminian,&nbsp;Elizabeth Snella,&nbsp;Jackie K. Jens,&nbsp;Sarah P. Young,&nbsp;Patricia I. Dickson,&nbsp;N. Matthew Ellinwood","doi":"10.1155/2023/7419017","DOIUrl":"10.1155/2023/7419017","url":null,"abstract":"<div>\u0000 <p>Mucopolysaccharidosis type I (MPS I), an inherited lysosomal storage disorder characterized by deficiency of <i>α</i>-<span>l</span>-iduronidase (IDUA) activity, causes multisystemic pathology due to sequelae of accumulated heparan and dermatan sulfates (HS and DS), the substrates of IDUA. Current treatments, though life-prolonging, inadequately address skeletal dysplasia and do not forestall progressive and painful degenerative joint disease. Previous studies demonstrated that intra-articular enzyme replacement cleared cellular lysosomal storage and reduced joint inflammation. Three nontolerized MPS I canines were studied to assess safety, efficacy, and durability of <i>IDUA</i> gene replacement therapy delivered via intra-articular injection. After baseline joint tissue biopsies, the right shoulder and stifle of each animal were injected in the intra-articular space with AAV9-<i>IDUA</i> and contralateral joints with AAV9-<i>eGFP</i>. Animals received either 5E11 or 5E12 vector genomes/joint. Necropsy was performed at 2- or 52-week postinjection. All animals tolerated injections without adverse effects. At two weeks, supraphysiologic IDUA enzyme activity was measured in AAV9-<i>IDUA</i>-treated but not AAV9-<i>eGFP</i>-treated synovium, with corresponding normalization of HS content and synoviocyte morphology. The AAV9-<i>IDUA-</i>treated cartilage had normal physiologic levels of IDUA enzyme, reduced but not normalized HS and DS levels compared to untreated MPS I cartilage, and healthy chondrocyte morphology. Liver <i>IDUA</i> transgene and IDUA enzyme activity were identified, as was serum IDUA activity which was 40% of wild-type serum enzyme activity. At 52-week postinjection, AAV9-<i>IDUA</i>-treated synovium and cartilage IDUA enzyme activity declined in both animals, corresponding to high tissue HS and DS levels and severe lysosomal storage. Liver and serum IDUA activity levels were undetectable. A dose-dependent serum anti-IDUA antibody response was observed which, together with loss of transgene with age, likely contributed to decline in tissue enzyme activity and treatment efficacy. Our study demonstrates successful proof-of-concept for intra-articular gene replacement therapy as a treatment for MPS-related joint dysplasia. Our observations suggest the possibility of multimodal gene replacement therapy to address multiple refractory manifestations of MPS I. Subsequent studies, in conjunction with immune tolerization and functional assessments of joint pathology, will investigate this possibility.</p>\u0000 </div>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"2023 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2023/7419017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135552550","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":"Diagnostic and Therapeutic Application of Proteomics in Infectious Disease","authors":"Fanuel Bizuayehu Yihunie,&nbsp;Mequanint Addisu Belete,&nbsp;Gizachew Fentahun,&nbsp;Solomon Getachew,&nbsp;Teshager Dubie","doi":"10.1155/2023/5510791","DOIUrl":"10.1155/2023/5510791","url":null,"abstract":"<div>\u0000 <p>The study of an organism’s genome, often known as “genomics,” has advanced quickly, producing a wealth of publicly accessible genetic data. Despite how valuable the genome is; proteins essentially control most aspects of cell function. Proteomics, or the comprehensive study of proteins, has emerged as an important technology for disease characterization, diagnosis, prognosis, drug development, and therapy. Proteomics technologies are now used to support the diagnosis and treatment of both infectious and noninfectious diseases. Nevertheless, it is more difficult to describe a proteomic profile since a single gene product may result in a number of unique proteins, and proteins have a wider range of chemical configurations. The proteome profiles of a particular organism, tissue, or cell are impacted by a variety of environmental factors, including those triggered by infectious agents. This review intends to highlight the applications of proteomics in the study of disease diagnosis and treatment. In this review, the different technologies used in proteomics studies, like two-dimensional gel electrophoresis, mass spectrometry, and protein microarray as well as biomarker discovery and drug target identification using proteomics, have also been focused on.</p>\u0000 </div>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"2023 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2023/5510791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43192073","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":"The Association between Genetic Variants and Gene Expression in RAAS Genes Using Captive-Bred Vervet Monkeys (Chlorocebus aethiops)","authors":"Sanele Khoza,&nbsp;Meenu Ghai,&nbsp;Chesa G. Chauke,&nbsp;Zandisiwe E. Magwebu","doi":"10.1155/2023/6344652","DOIUrl":"10.1155/2023/6344652","url":null,"abstract":"<div>\u0000 <p>Mendelian genetics contribute largely to the development of hypertension; therefore, the identification of genetic variants related to blood pressure (BP) regulation remains crucial and may reveal new therapeutic drug targets. The purpose of the present study was to screen the captive-bred Vervet colony for salt-sensitive sequence variants or single nucleotide polymorphisms (SNPs) in the selected Renin-Angiotensin-Aldosterone System (RAAS) genes associated with salt sensitivity. Blood samples were collected from 16 captive-bred Vervet monkeys for genotyping and gene expression analysis. The impact of the identified sequence variants was determined using online prediction tools. Sanger sequencing analysis revealed 21 sequence variants in <i>AGT</i>, <i>CYP3A5</i>, <i>GRK4</i>, and <i>SCL4A5</i>, of which 19 were novel and two were previously reported in humans. All novel variants were either predicted to be polymorphic, disease-causing, or possibly damaging by prediction tools. Furthermore, the mRNA expression for <i>AGT</i> was significantly higher in the normal BP group (<i>p</i> value = 0.02), and a similar trend was observed for <i>CYP3A5</i> and <i>GRK4</i>, whereas <i>SCL4A5</i> was higher in the hypertensive group. The identified salt-sensitive variants specifically in <i>GRK4</i> may be suggestive to be the attributing factor of the elevated BP levels in these captive-bred Vervet monkeys. Therefore, RAAS variants could be considered as a biomarker to identify the potential risk of developing hypertension in both humans and nonhuman primates.</p>\u0000 </div>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"2023 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2023/6344652","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43843574","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}