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Universal Anti-CD7 CAR-T Cells Targeting T-ALL and Functional Analysis of CD7 Antigen on T/CAR-T Cells. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-11-24 Leling Xie,Runxia Gu,Xue Yang,Shaowei Qiu,Yingxi Xu,Junli Mou,Ying Wang,Haiyan Xing,Kejing Tang,Zheng Tian,Qing Rao,Min Wang,Jianxiang Wang
Chimeric antigen receptor T (CAR-T) cell therapy initiates new methods and turns the scale of clinical treatment on relapsed/refractory acute T lymphoblastic leukemia (T-ALL). In this study, we generated the second-generation CD7-targeting CAR-T cells with a new antigen-binding single-chain variable fragment sequence and made it universal via CRISPR-based knockout of TRAC and CD7 genes (termed UCAR-T)
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The Lived Experience of Pediatric Gene Therapy - A Scoping Review. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-11-15 Laura Kimberly,Cara Hunt,Katherine Beaverson,Emma James,Alison Bateman-House,Richard McGowan,Jennifer DeSante-Bertkau
Little is known about patients' and families' lived experience of participating in pediatric gene therapy (GT) clinical trials. Currently, pediatric GT research targets a broad range of indications--including rare and ultra-rare diseases--which vary in severity and in the availability of alternative therapies. Pediatric GT differs meaningfully from adult GT because the decision to participate involves
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Prevalent and Disseminated Recombinant and Wild-Type Adeno-Associated Virus Integration in Macaques and Humans. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-11-06 Kelly M Martins,Camilo Breton,Qi Zheng,Zhe Zhang,Caitlin Latshaw,Jenny A Greig,James M Wilson
Integration of naturally occurring adeno-associated viruses (AAV; wild-type AAV [wtAAV]) and those used in gene therapy (recombinant AAV [rAAV]) into host genomic DNA has been documented for over two decades. Results from mouse and dog studies have raised concerns of insertional mutagenesis and clonal expansion following AAV exposure, particularly in the context of gene therapy. This study aimed to
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Integration of Gene Therapy Vectors: A Risk Factor for Tumorigenesis or Another Commensal Property of Adeno-Associated Viruses That Benefits Long-Term Transgene Expression? Hum. Gene Ther. (IF 4.2) Pub Date : 2023-11-06 Phillip W L Tai
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Engineered Human Adenoviruses of Species B and C Report Early, Intermediate Early, and Late Viral Gene Expression. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-11-06 Tania Jetzer,Lukas Studer,Manuela Bieri,Urs F Greber,Silvio Hemmi
Adenoviruses (AdVs) are being developed for oncolytic or vaccination therapy against existing and emerging conditions. Well-characterized replication-competent human and human primate AdVs expressing multiple payloads are desirable, but their replication in rodent models is limited. To score the timing of adenoviral gene expression in cell cultures, we developed fully replication-competent transcriptional
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First Prime Editing Clinical Trial Expected in 2024. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-11-01 Alex Philippidis
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A Recombinant Oncolytic Influenza Virus Carrying GV1001 Triggers an Antitumor Immune Response. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-10-30 Cong Li,Yuying Tian,Fang Sun,Guanglin Lei,Jinxia Cheng,Chongyu Tian,Hongyu Yu,Zhuoya Deng,Shuai Lu,Lishi Wang,Ruixue Xiao,Changqing Bai,Penghui Yang
Oncolytic viruses are able to lyse tumor cells selectively in the liver without killing normal hepatocytes, in addition to activating the immune response. Oncolytic virus therapy is expected to revolutionize the treatment of liver cancer, including hepatocellular carcinoma (HCC), one of the most frequent and fatal malignancies. In this study, reverse genetics techniques were exploited to load NA fragments
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Development and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method for Sensitive Analysis of Residual Protein Tat Bh1-101 in Lentiviral Vectors for Gene Therapy. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-10-26 Yan Lu,Chao-Xuan Zhang,Patrick Rodrigues,Lei Yang,Aaron Shafer,Zoran Rankovic,Frank Fazio
Lentiviral (LV) vector-based gene therapy is gaining popularity for treating a wide range of diseases. Various LV vectors are being developed for transducing cells in cellular gene therapy at St. Jude. Some LV vectors are produced using stable 293T packaging cell lines, which includes gag-pol-rev-tat and virus-glycoprotein. Transactivating factor (transactivator of transcription [Tat]) is a regulatory
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Positron Emission Tomography Quantitative Assessment of Off-Target Whole-Body Biodistribution of I-124-Labeled Adeno-Associated Virus Capsids Administered to Cerebral Spinal Fluid. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-10-23 Jonathan B Rosenberg,Edward K Fung,Jonathan P Dyke,Bishnu P De,Howard Lou,James M Kelly,Layla Reejhsinghani,Rodolfo J Ricart Arbona,Dolan Sondhi,Stephen M Kaminsky,Nathalie Cartier,Christian Hinderer,Juliette Hordeaux,James M Wilson,Douglas J Ballon,Ronald G Crystal
Based on studies in experimental animals demonstrating that administration of adeno-associated virus (AAV) vectors to the cerebrospinal fluid (CSF) is an effective route to transfer genes to the nervous system, there are increasing number of clinical trials using the CSF route to treat nervous system disorders. With the knowledge that the CSF turns over four to five times daily, and evidence in experimental
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Prevention of Portal-Tract Fibrosis in Zfyve19-/- Mouse Model with Adeno-Associated Virus Vector Delivering ZFYVE19. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-10-18 Yanan Zhang,Dingyue Tang,Li Wang,Jing Yang,Xia Wu,Xiao Xiao,Jian-She Wang
Zinc finger FYVE-type containing 19 (ZFYVE19) deficiency, caused by biallelic ZFYVE19 complete loss-of-function variants, is a recently identified chronic hepatobiliary disorder characterized by obvious portal-tract fibrosis, increased numbers of bile ducts with malformations, and abnormal levels of serum markers of hepatobiliary injury. As liver-targeted adeno-associated virus (AAV) gene therapy has
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Adeno-Associated Viral Vector-Delivered Pannexin-1 Mimetic Peptide Alleviates Airway Inflammation in an Allergen-Sensitized Mouse Model. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-10-18 Yung-An Huang,Jeng-Chang Chen,Pei-Chuan Chiang,Li-Chen Chen,Ming-Ling Kuo
Asthma is a chronic inflammatory disease around the world. Extracellular adenosine triphosphate works as a dangerous signal in responding to cellular stress, irritation, or inflammation. It has also been reported its association with the pathogenicity in asthma, with increased level in lungs of asthmatics. Pannexin-1 is one of the routes that contributes to the release of adenosine triphosphate form
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Clustered Regularly Interspaced Short Palindromic Repeats and Clustered Regularly Interspaced Short Palindromic Repeats-Associated Protein 9 System: Factors Affecting Precision Gene Editing Efficiency and Optimization Strategies. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-10-17 Jiawen Li,Chuxi Tang,Guozheng Liang,Huiqun Tian,Guanxi Lai,Yixiang Wu,Shiwen Liu,Wenfeng Zhang,Song Liu,Hongwei Shao
The clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated (Cas) system is a powerful genomic DNA editing tool. The increased applications of gene editing tools, including the CRISPR-Cas system, have contributed to recent advances in biological fields, such as genetic disease therapy, disease-associated gene screening and detection, and cancer therapy. However, the major
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Transduction of Ferret Surface and Basal Cells of Airways, Lung, Liver, and Pancreas via Intratracheal or Intravenous Delivery of Adeno-Associated Virus 1 or 6. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-10-16 Murali K Yanda,Adi Zeidan,Cristian Ciobanu,Jessica Izzi,William B Guggino,Liudmila Cebotaru
Cystic fibrosis (CF) is potentially treatable by gene therapy. Since the identification of the CF gene, preclinical and clinical trials have concentrated on achieving effective gene therapy targeting the lung. However, the lung has proven to be a formidable barrier to successful gene therapy especially for CF, and many clinical trials failed to achieve efficacy. Recent advances in vector design and
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Cure Rare Disease: An Initiative to Enable N of 1 Gene Editing. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-10-12 Richard W Horgan
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What We Owe Terry Horgan: Reflections from Providers, Family, and Scientists. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-10-12
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Special Editorial Feature: Learning from Our Failures. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-10-12 Terence R Flotte
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Significant Differences in Capsid Properties and Potency Between Adeno-Associated Virus Vectors Produced in Sf9 and HEK293 Cells. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-10-04 April Giles,Martin Lock,Shu-Jen Chen,Kevin Turner,Gregg Wesolowski,Andrew Prongay,Boris N Petkov,Kanyin Olagbegi,Hanying Yan,James M Wilson
For successful vector-based gene therapy manufacturing, the selected adeno-associated virus (AAV) vector production system must produce vector at sufficient scale. However, concerns have arisen regarding the quality of vector produced using different systems. In this study, we compared AAV serotypes 1, 8, and 9 produced by two different systems (Sf9/baculovirus and HEK293/transfection) and purified
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Kallistatin Improves High-Fat-Induced Insulin Resistance via Epididymal Adipose Tissue-Derived Exosomes. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-10-04 Zi-Wei Yang,Jing-Jing Ji,Yu Jiang,Ya Wu,Jia-Qi Guo,Gen-Shan Ma,Yu-Yu Yao
Objective: Studies have found that high expression of human Kallistatin (HKS) in adipose tissue can improve obesity and its associated comorbidities, but the underlying mechanism of specific regulation is unclear. Methods: An obesity model was built by injecting 8-week-old C57BL/6 mice (n = 6 mice per group) with Ad.Null and Ad.HKS adenovirus into epididymal adipose tissue and fed with a high-fat diet
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Up to $1.5B in Milestones as Otsuka, Shape Partner on Eye Disease Gene Therapies. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-10-01 Alex Philippidis
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Gene Therapy for Immunoglobulin E, Complement-Mediated, and Eosinophilic Disorders. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-10-01 Odelya E Pagovich,Ronald G Crystal
Immunoglobulin E, complement, and eosinophils play an important role in host defense, but dysfunction of each of these components can lead to a variety of human disorders. In this review, we summarize how investigators have adapted gene therapy and antisense technology to modulate immunoglobulin E, complement, and/or eosinophil levels to treat these disorders.
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How Great a Risk Do You Take? A Qualitative Study Exploring Attitudes of Individuals with Friedreich Ataxia Toward Gene Therapy. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-10-01 Katherine Lieschke,Varlli Scott,Martin B Delatycki,Sharon Lewis,Megan Munsie,Claire Tanner,Louise A Corben
Scientists and pharmaceutical companies are working toward delivering gene therapy (GT) for Friedreich ataxia (FRDA). Understanding the views of people with lived experience of FRDA and their parents toward GT is essential to inform trial design and identify potential barriers to participation in clinical trials. The goals of this study were to identify the attitudes toward GT held by individuals with
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Developing a Gene Therapy for the Treatment of Autosomal Dominant Alzheimer's Disease. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-10-01 Benjamin Moore,Apurwa Sharma,Martin Goulet,Tracey Suter,Carolyn Pelletier,Ruoxi Hu,Eric Schaeffer,Raymond J Kelleher
Autosomal dominant Alzheimer's disease (ADAD) is a rare early-onset form of Alzheimer's disease, caused by dominant mutations in one of three genes: presenilin 1, presenilin 2, and amyloid β precursor protein (APP). Mutations in the presenilin 1 gene (PSEN1) account for the majority of cases, and individuals who inherit a single-mutant PSEN1 allele go on to develop early-onset dementia, ultimately
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Enhanced Cochlear Transduction by AAV9 with High-Concentration Sucrose. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-09-29 Masao Noda,Ryota Koshu,Mari Shimada Dias,Chizu Saito,Naomi Takino,Mika Ito,Hidekane Yoshimura,Makoto Ito,Shin-Ichi Muramatsu
The inner ear is a primary lesion in sensorineural hearing loss and has been a target in gene therapy. The efficacy of gene therapy depends on achieving sufficient levels of transduction at a safe vector dose. Vectors derived from various adeno-associated viruses (AAVs) are predominantly used to deliver therapeutic genes to inner ear cells. AAV9 and its variants vector are attractive candidates for
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Drug Repositioning for Amyloid Transthyretin Amyloidosis by Interactome Network Corrected by Graph Neural Networks and Transcriptome Analysis. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-11-27 Shan He,XiaoYing Lv,XinYue He,JinJiang Guo,RuoKai Pan,YuTong Jin,Zhuang Tian,LuRong Pan,ShuYang Zhang
Amyloid transthyretin (ATTR) amyloidosis caused by transthyretin misfolded into amyloid deposits in nerve and heart is a progressive rare disease. The unknown pathogenesis and the lack of therapy make the 5-year survival prognosis extremely poor. Currently available ATTR drugs can only relieve symptoms and slow down progression, but no drug has demonstrated curable effect for this disease. The growing
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Clinical Efficacy and Safety of AdV-tk Gene Therapy for Patients with Cervical Squamous Intraepithelial Lesion: A Prospective Study. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-09-05 Nan Wang,Xiulan Li,Xin Liu,Meina Bian,Ying Hou,Yuxiang Zhou,Yanmei Li,Fuqiang Xu,Huadong Tang,Ning Li,Qing Liu
Cervical cancer is the fourth most common type of cancer for women in 2020, and many more women have cervical precancerous lesion-squamous intraepithelial lesion (SIL). Early treatment of cervical SIL to reverse or delay its progression is an important approach to reduce the incidence of cervical cancer. The efficacy and safety of adenovirus-based vectors expressing the thymidine kinase gene (AdV-tk)
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Ultragenyx Gene Therapies Spark Lawsuit from Lacks Family. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-09-01 Alex Philippidis
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Genome Editing in Engineered T Cells for Cancer Immunotherapy. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-09-01 Chiara Bonini,Aude G Chapuis,Michael Hudecek,Sonia Guedan,Chiara Magnani,Waseem Qasim
Advanced gene transfer technologies and profound immunological insights have enabled substantial increases in the efficacy of anticancer adoptive cellular therapy (ACT). In recent years, the U.S. Food and Drug Administration and European Medicines Agency have approved six engineered T cell therapeutic products, all chimeric antigen receptor-engineered T cells directed against B cell malignancies. Despite
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Advances and Challenges in the Development of Gene Therapy Medicinal Products for Rare Diseases. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-09-01 Juan A Bueren,Alberto Auricchio
The development of viral vectors and recombinant DNA technology since the 1960s has enabled gene therapy to become a real therapeutic option for several inherited and acquired diseases. After several ups and downs in the gene therapy field, we are currently living a new era in the history of medicine in which several ex vivo and in vivo gene therapies have reached maturity. This is testified by the
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Hemophilia Gene Therapy: The End of the Beginning? Hum. Gene Ther. (IF 4.2) Pub Date : 2023-09-01 Dries De Wolf,Kshitiz Singh,Marinee K Chuah,Thierry VandenDriessche
Extensive preclinical research over the past 30 years has culminated in the recent regulatory approval of several gene therapy products for hemophilia. Based on the efficacy and safety data in a recently conducted phase III clinical trial, Roctavian® (valoctocogene roxaparvovec), an adeno-associated viral (AAV5) vector expressing a B domain deleted factor VIII (FVIII) complementary DNA, was approved
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Understanding and Tackling Immune Responses to Adeno-Associated Viral Vectors. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-09-01 Helena Costa-Verdera,Carmen Unzu,Erika Valeri,Sahil Adriouch,Gloria González Aseguinolaza,Federico Mingozzi,Anna Kajaste-Rudnitski
As the clinical experience in adeno-associated viral (AAV) vector-based gene therapies is expanding, the necessity to better understand and control the host immune responses is also increasing. Immunogenicity of AAV vectors in humans has been linked to several limitations of the platform, including lack of efficacy due to antibody-mediated neutralization, tissue inflammation, loss of transgene expression
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Limitations of Dual-Single Guide RNA CRISPR Strategies for the Treatment of Central Nervous System Genetic Disorders. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-09-01 Fábio Duarte,Gabriel Vachey,Nicholas S Caron,Melanie Sipion,Maria Rey,Anselme L Perrier,Michael R Hayden,Nicole Déglon
Huntington's disease (HD) is a fatal neurodegenerative disorder caused by a toxic gain-of-function CAG expansion in the first exon of the huntingtin (HTT) gene. The monogenic nature of HD makes mutant HTT (mHTT) inactivation a promising therapeutic strategy. Single nucleotide polymorphisms frequently associated with CAG expansion have been explored to selectively inactivate mHTT allele using the CRISPR/Cas9
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The Opportunities and Challenges of Gene Therapy for Treatment of Inherited Forms of Vision and Hearing Loss. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-09-01 Emmanuel J Simons,Ivana Trapani
Inherited forms of blindness and deafness are highly prevalent and severe conditions that significantly impact the lives of millions of people worldwide. The lack of therapeutic options for these conditions poses a major socioeconomic burden. Over the last decades, gene therapy has proven to be a life changing treatment for hereditary and acquired forms of diseases, and extensive preclinical investigation
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Recent Advances Using Genetic Therapies Against Infectious Diseases and for Vaccination. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-09-01 Anne Galy,Ben Berkhout,Karine Breckpot,Chantal Pichon,Kristie Bloom,Hans-Peter Kiem,Michael D Mühlebach,Joseph M McCune
The development of prophylatic or therapeutic medicines for infectious diseases is one of the priorities for health organizations worldwide. Innovative solutions are required to achieve effective, safe, and accessible treatments for most if not all infectious diseases, particularly those that are chronic in nature or that emerge unexpectedly over time. Genetic technologies offer versatile possibilities
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Realizing the Potential of Gene Therapies for Rare and Ultra-Rare Inherited Diseases. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-09-01 Claire Booth,Alessandro Aiuti
Rare and ultrarare diseases have been central to the field of gene therapy since its earliest stage, and we are now witnessing more and more effective treatments entering the clinical realm for patients in need. However, despite promising results across a range of rare diseases, transformative gene therapies may not be available and accessible to patients for nonmedical reasons. Traditional regulatory
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Assessment of Safety and Biodistribution of AAVrh.10hCLN2 Following Intracisternal Administration in Nonhuman Primates for the Treatment of CLN2 Batten Disease. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-09-01 Bishnu P De,Jonathan B Rosenberg,Nithya Selvan,Isabelle Wilson,Nadir Yusufzai,Alessandria Greco,Stephen M Kaminsky,Linda A Heier,Rodolfo J Ricart Arbona,Ileana C Miranda,Sebastien Monette,Anju Nair,Richie Khanna,Ronald G Crystal,Dolan Sondhi
CLN2 disease is a fatal, childhood autosomal recessive disorder caused by mutations in ceroid lipofuscinosis type 2 (CLN2) gene, encoding tripeptidyl peptidase 1 (TPP-1). Loss of TPP-1 activity leads to accumulation of storage material in lysosomes and resultant neuronal cell death with neurodegeneration. Genotype/phenotype comparisons suggest that the phenotype should be ameliorated with increase
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Restoring Ciliary Function: Gene Therapeutics for Primary Ciliary Dyskinesia. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-09-01 Nicholas W Keiser,Erin Cant,Sneha Sitaraman,Amelia Shoemark,Maria P Limberis
Primary ciliary dyskinesia (PCD) is a genetic disease characterized by defects in motile cilia, which play an important role in several organ systems. Lung disease is a hallmark of PCD, given the essential role of cilia in airway surface defense. Diagnosis of PCD is complicated due to its reliance on complex tests that are not utilized by every clinic and also its phenotypic overlap with several other
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Chemical Epigenetic Regulation of Adeno-Associated Virus Delivered Transgenes. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-09-01 Jessica D Umaña,Sara R Wasserman,Liujiang Song,Arushi A Goel,Xufen Yu,Jian Jin,Nathaniel A Hathaway
Adeno-associated virus (AAV) is a powerful gene therapy vector that has been used in several FDA-approved therapies as well as in multiple clinical trials. This vector has high therapeutic versatility with the ability to deliver genetic payloads to a variety of human tissue types, yet there is currently a lack of transgene expression control once the virus is administered. There are also times when
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Preclinical Development and Characterization of Novel Adeno-Associated Viral Vectors for the Treatment of Lipoprotein Lipase Deficiency. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-09-01 Neel Mehta,Rénald Gilbert,Parminder S Chahal,Maria J Moreno,Nasha Nassoury,Nathalie Coulombe,Viktoria Lytvyn,Mario Mercier,Dorothy Fatehi,Wendy Lin,Emily M Harvey,Lin-Hua Zhang,Nazila Nazemi-Moghaddam,Seyyed Mehdy Elahi,Colin J D Ross,Danica B Stanimirovic,Michael R Hayden
Lipoprotein lipase deficiency (LPLD) results from mutations within the lipoprotein lipase (LPL) gene that lead to a complete lack of catalytically active LPL protein. Glybera was one of the first adeno-associated virus (AAV) gene replacement therapy to receive European Medicines Agency regulatory approval for the treatment of LPLD. However, Glybera is no longer marketed potentially due to a combination
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Viral Vectors Expressing Interleukin 2 for Cancer Immunotherapy. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-09-01 Hongbin Wang,Mia Borlongan,Akseli Hemminki,Saru Basnet,Naresh Sah,Howard L Kaufman,Samuel D Rabkin,Dipongkor Saha
Interleukin 2 (IL-2) plays a crucial role in T cell growth and survival, enhancing the cytotoxic activity of natural killer and cytotoxic T cells and thus functioning as a versatile master proinflammatory anticancer cytokine. The FDA has approved IL-2 cytokine therapy for the treatment of metastatic melanoma and metastatic renal cell carcinoma. However, IL-2 therapy has significant constraints, including
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Biotechnological Advances in Gene Therapy of Hematopoietic Stem Cells: Systematic Review and Meta-Analysis. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-11-01 Carla Cristina Pedrosa de Lira de Morais,Daniela Prado Cunha,Zilton Farias Meira de Vasconcelos
Gene therapy (GT) has emerged as a promising treatment option for disorders in the hematopoietic system, particularly primary immunodeficiencies (PID). Hematopoietic stem cells (HSCs) have gained attention due to their ability to support long-term hematopoiesis. In this study, we present a summary of research evaluating the most effective method of gene editing in HSCs for translational medicine. We
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BioMarin's ROCTAVIAN Wins Food and Drug Administration Approval As First Gene Therapy for Severe Hemophilia A. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-08-01 Alex Philippidis
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Effects of Urocortin 2 Gene Transfer on Glucose Disposal in Insulin-Resistant db/db Mice on Metformin. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-07-11 Mei Hua Gao,Dimosthenis Giamouridis,N Chin Lai,Tracy Guo,H Kirk Hammond
The study was designed to determine whether urocortin 2 (Ucn2) gene transfer is as safe and effective as metformin in insulin-resistant mice. Four groups of insulin-resistant db/db mice and a nondiabetic group were studied: (1) metformin; (2) Ucn2 gene transfer; (3) metformin + Ucn2 gene transfer; (4) saline; and (5) nondiabetic mice. After completion of the 15-week protocol, glucose disposal was quantified
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Establishment of the Effectiveness of Early Versus Late Stem Cell Gene Therapy in Mucopolysaccharidosis II for Treating Central Versus Peripheral Disease. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-08-30 Oriana Mandolfo,Aiyin Liao,Esha Singh,Claire O'leary,Rebecca J Holley,Brian W Bigger
Mucopolysaccharidosis type II (MPSII) is a rare pediatric X-linked lysosomal storage disease, caused by heterogeneous mutations in the iduronate-2-sulfatase (IDS) gene, which result in accumulation of heparan sulfate (HS) and dermatan sulfate within cells. This leads to severe skeletal abnormalities, hepatosplenomegaly, and cognitive deterioration. The progressive nature of the disease is a huge obstacle
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Artificial Downregulation of Ribosomal Protein L34 Restricts the Proliferation and Metastasis of Colorectal Cancer by Suppressing the JAK2/STAT3 Signaling Pathway. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-08-01 Yi-Chao Liang,Rui Li,Shu-Rui Bao,Zhi-Long Li,Hong-Zhuan Yin,Chao-Liu Dai
The highly conserved ribosomal protein L34 (RPL34) has been reported to play an essential role in the progression of diverse malignancies. RPL34 is aberrantly expressed in multiple cancers, although its significant in colorectal cancer (CRC) is currently unclear. Here, we demonstrated that RPL34 expression was higher in CRC tissues than in normal tissues. Upon RPL34 overexpression, the ability of proliferation
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Identification of Safe and Effective Intravenous Dose of AAVrh.10hFXN to Treat the Cardiac Manifestations of Friedreich's Ataxia. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-07-04 Carlos Munoz-Zuluaga,Monica Gertz,Melissa Yost-Bido,Alessandria Greco,Nicholas Gorman,Alvin Chen,Vikrum Kooner,Jonathan B Rosenberg,Bishnu P De,Stephen M Kaminsky,Alain Borczuk,Rodolfo J Ricart Arbona,Heather R Martin,Sebastien Monette,Richie Khanna,Jay A Barth,Ronald G Crystal,Dolan Sondhi
Friedreich's ataxia (FA) is a life-threatening autosomal recessive disorder characterized by neurological and cardiac dysfunction. Arrhythmias and heart failure are the main cause of premature death. From prior studies in murine models of FA, adeno-associated virus encoding the normal human frataxin gene (AAVrh.10hFXN) effectively treated the cardiac manifestations of the disease. However, the therapeutic
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Case Study Cites Immune Reaction to High Adeno-Associated Virus Dose in Explaining Duchenne Muscular Dystrophy Trial Death. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-07-01 Alex Philippidis
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Advances in Split Vector Approaches for Adeno-Associated Virus Gene Therapy. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-07-01 Feng Gu
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An Engineered Adeno-Associated Virus Capsid Mediates Efficient Transduction of Pericytes and Smooth Muscle Cells of the Brain Vasculature. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-08-01 Servio H Ramirez,Jonathan F Hale,Siobhan McCarthy,Christian L Cardenas,Kalpani N Udeni Galpayage Dona,Killian S Hanlon,Eloise Hudry,Demitri De La Cruz,Carrie Ng,Sabyasachi Das,Diane M Nguyen,Josette Nammour,Rachel E Bennett,Allison M Andrews,Patricia L Musolino,Casey A Maguire
Neurodegeneration and cerebrovascular disease share an underlying microvascular dysfunction that may be remedied by selective transgene delivery. To date, limited options exist in which cellular components of the brain vasculature can be effectively targeted by viral vector therapeutics. In this study, we characterize the first engineered adeno-associated virus (AAV) capsid mediating high transduction
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Recapitulation of Skewed X-Inactivation in Female Ornithine Transcarbamylase-Deficient Primary Human Hepatocytes in the FRG Mouse: A Novel System for Developing Epigenetic Therapies. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-09-11 Sharon C Cunningham,Eva B van Dijk,Erhua Zhu,Maya Sugden,Mawj Mandwie,Susan Siew,Beena Devanapalli,Adviye Ayper Tolun,Anne Klein,Laurence Wilson,Nader Aryamanesh,Paul Gissen,Julien Baruteau,Kaustuv Bhattacharya,Ian E Alexander
Realization of the immense therapeutic potential of epigenetic editing requires development of clinically predictive model systems that faithfully recapitulate relevant aspects of the target disease pathophysiology. In female patients with ornithine transcarbamylase (OTC) deficiency, an X-linked condition, skewed inactivation of the X chromosome carrying the wild-type OTC allele is associated with
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Genome Editing in Ferret Airway Epithelia Mediated by CRISPR/Nucleases Delivered with Amphiphilic Shuttle Peptides. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-07-20 Meihui Luo,Jia Ma,Xue Cheng,Shuang Wu,Douglas J Bartels,David Guay,John F Engelhardt,Xiaoming Liu
Gene editing strategies are attractive for treating genetic pulmonary diseases such as cystic fibrosis (CF). However, challenges have included the development of safe and effective vector systems for gene editing of airway epithelia and model systems to report their efficiency and durability. The domestic ferret (Mustela putorius furo) has a high degree of conservation in lung cellular anatomy with
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Screening an Effective Dual-Adeno-Associated Virus Split-Cytosine Base Editor System for C-to-T Conversion In Vivo. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-07-01 Qianyi Liu,Yuxi Chen,Sihui Hu,Weiliang Liu,Dongchun Xie,Xin Yang,Wenyan Huang,Simiao Liu,Xiaolin Chen,Haiying Liu,Junjiu Huang
The cytosine base editor (CBE) has shown promise as a gene editing tool for gene therapy, as it can convert cytidine to thymidine. Adeno-associated virus (AAV) has been widely used for in vivo gene therapy, but its limited 4.7 kb packing capacity presents challenges in delivering CBE by a single AAV. To address this, one feasible solution is to split CBE into two sections for dual-AAV delivery. In
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CRISPR-Mediated Base Editing: Promises and Challenges for a Viable Oncotherapy Strategy. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-07-20 Lu Huang,Chao Yang,Yan Chen,Han Deng,Zhi Liao,Hongtao Xiao
Base editing technology, developed from the CRISPR/Cas9 system, is able to efficiently implement single-base substitutions at specific DNA or RNA sites without generating double-strand breaks with precision and efficiency. Point mutations account for 58% of disease-causing genetic mutations in humans, and single nucleotide variants are an important cause of tumorigenesis, and the advent of base editors
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Improvement of Precision in Recombinant Adeno-Associated Virus Infectious Titer Assay with Droplet Digital PCR as an Endpoint Measurement. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-07-04 Tam Duong,James McAllister,Khalid Eldahan,Jennifer Wang,Eric Onishi,Kate Shen,Robert Schrock,Bingnan Gu,Peng Wang
Recombinant adeno-associated virus (rAAV) has been utilized successfully for in vivo gene delivery for treatment of a variety of human diseases. To sustain the growth of recombinant AAV gene therapy products, there is a critical need for the development of accurate and robust analytical methods. Fifty percent tissue culture infectious dose (TCID50) assay is an in vitro cell-based method widely used
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Characteristics, Recombination Methods, and Applications Progresses of Split-Cas9 System. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-07-04 Zhixi Liu,Lu Huang,Han Deng,Yan Chen,Hongtao Xiao
CRISPR technology has been used to revolutionize various facets of life sciences because of its potent gene editing capabilities. In particular, CRISPR technology is anticipated to be used to cure congenital disorders, and malignant cancers brought on by gene mutation. In this article, we introduce a Split-Cas9 system, in which Cas9 protein is split into two or more parts and recombined in cells to
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Food and Drug Administration Sets Stage for Approval of First Duchenne Muscular Dystrophy Gene Therapy. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-06-01 Alex Philippidis
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Long Non-Coding RNAs, Cell Cycle, and Human Breast Cancer. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-06-01 Qinan Yin,Haodi Ma,Gayan Bamunuarachchi,Xuewei Zheng,Yan Ma
The long non-coding RNAs (lncRNAs) constitute an important class of the human transcriptome. The discovery of lncRNAs provided one of many unexpected results of the post-genomic era and uncovered a huge number of previously ignored transcriptional events. In recent years, lncRNAs are known to be linked with human diseases, with particular focus on cancer. Growing evidence has indicated that dysregulation
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Split AAV8 Mediated ABCA4 Expression for Gene Therapy of Mouse Stargardt Disease (STGD1). Hum. Gene Ther. (IF 4.2) Pub Date : 2023-07-01 Ruiting Li,Qiuping Jing,Kaiqin She,Qingnan Wang,Xiu Jin,Qinyu Zhao,Jing Su,Li Song,Jiamei Fu,Xiaoyi Wu,Qiuxia Xu,Fang Lu,Yuquan Wei,Yang Yang
Adeno-associated virus (AAV)-based gene therapy has been shown to be safe and effective in numerous animal models and clinical trials for various ophthalmic diseases. Stargardt disease (STGD1; MIM #248200) is the most common autosomal recessive macular dystrophy disease, and the most common form is caused by mutations in the ABCA4 gene, a gene with 6.8 kb coding sequence. Split intein approaches increase
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Fusion of Rabies Virus Glycoprotein or gh625 to Iduronate-2-Sulfatase for the Treatment of Mucopolysaccharidosis Type II. Hum. Gene Ther. (IF 4.2) Pub Date : 2023-07-07 Shaun R Wood,Ahsan Chaudrhy,Stuart Ellison,Rachel Searle,Constance Burgod,Ghazala Tehseen,Gabriella Forte,Claire O'Leary,Hélène Gleitz,Aiyin Liao,James Cook,Rebecca Holley,Brian W Bigger
Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disease caused by a mutation in the IDS gene, resulting in deficiency of the enzyme iduronate-2-sulfatase (IDS) causing heparan sulfate (HS) and dermatan sulfate (DS) accumulation in all cells. This leads to skeletal and cardiorespiratory disease with severe neurodegeneration in two thirds of sufferers. Enzyme replacement therapy is ineffective