Establishment of a novel human amniotic epithelial-derived cell line, HAT, for high-yield AAV vector production [0.03%]
建立一个新型的人胎盘绒毛膜上皮细胞系HAT用于高产AAV载体生产
Yugo Hirai,Yu-Hsin Chang,Arisa Yamamoto et al.
Yugo Hirai et al.
Gene therapy using adeno-associated virus (AAV) vectors has advanced remarkably in recent decades. However, efficient AAV vector production remains challenging despite extensive efforts to optimize the commonly used HEK293 cells. Here, we d...
Comparative analysis of cell-specific promoters in AAV9-mediated gene therapy targeting the central nervous system [0.03%]
AAV9介导的基因治疗靶向中枢神经系统的细胞特异性启动子的比较分析研究
Sergiy Chornyy,Jessica A Herstine,Caleb Holaway et al.
Sergiy Chornyy et al.
We present a comprehensive toolkit of ubiquitous and cell-specific promoters for potential use in adeno-associated virus (AAV)9-mediated gene therapy for central nervous system (CNS) disorders, systematically evaluating biodistribution, cel...
Functional, sustained recovery of hearing in Otoferlin-deficient mice using DB-OTO, a hair-cell-specific AAV-based gene therapy [0.03%]
一种基于腺相关病毒的基因疗法使Otoferlin缺陷小鼠恢复了持续性的听力功能
Yoojin Chung,Seth D Koehler,Sarah Cancelarich et al.
Yoojin Chung et al.
Biallelic loss-of-function variants in the Otoferlin gene (OTOF) lead to congenital hearing loss in both humans and mice. We developed DB-OTO, a hair-cell-specific adeno-associated virus (AAV)-based dual-vector gene therapy designed to rest...
Variation of VP2 stoichiometry and deamidation of VP1 during production and their impacts on the transduction efficiency of AAV vectors [0.03%]
衣壳VP2比例变化和VP1脱氨基对AAV载体转导效率的影响研究
Takahiro Maruno,Mitsuko Fukuhara,Yasuo Tsunaka et al.
Takahiro Maruno et al.
Recombinant adeno-associated viruses (rAAVs) are a leading platform for in vivo gene therapy. However, limited information is available on the fluctuation of quality attributes (QAs), during manufacturing using the HEK293 suspension cell li...
Adeno-associated viral vector resource for the RNA-targeting Cas13d: A comparison of high-fidelity variants, DjCas13d and hfCas13d [0.03%]
针对RNA靶向Cas13d的腺相关病毒载体资源：高保真变异体DjCas13d和hfCas13d的比较
Franklin Back,Alfredo Sandoval,Lily M Vu et al.
Franklin Back et al.
RNA-targeting CRISPR-Cas systems have emerged as alternatives to RNA-interference technology to knock down specific RNA transcripts. In particular, Cas13d derived from Ruminococcus flavefaciens (CasRx, RfxCas13d) has generated interest due ...
Ming Yang,Sana Shaheen,Keying Yang et al.
Ming Yang et al.
Replication-competent adeno-associated virus (rcAAV) content is a crucial contaminant in the process of recombinant adeno-associated virus (rAAV) production in gene therapy products, from preclinical to clinical stages. The gold standard fo...
pH-dependent DNA degradation pathways for adeno-associated virus gene therapy [0.03%]
用于腺相关病毒基因治疗的pH依赖性DNA降解途径
Jefferson S Plegaria,Kimberly A Malecka,Qi Lin et al.
Jefferson S Plegaria et al.
Adeno-associated virus (AAV) vector genome degradation mechanisms that reduce transduction efficiency and viral potency must be understood to define critical quality attributes to ensure safety and efficacy. Here, we report that under prolo...
Design of cationic ionizable lipids for the delivery of therapeutic nucleic acids [0.03%]
阳离子可电离脂质的设计用于治疗性核酸的输送
N D Prasad Atmuri,Fariba Saadati,Jayesh Kulkarni et al.
N D Prasad Atmuri et al.
Ionizable cationic lipids are a critical component of lipid nanoparticles (LNPs), enabling the clinical success of nucleic acid therapeutics through effective encapsulation, delivery, and release. As the field accelerates beyond first-gener...
CAR T cell engineering impacts antigen-independent activation and co-inhibition [0.03%]
CAR-T细胞工程影响抗原非依赖性活化和协同抑制
Christoph Schultheiß,Simon Stücheli,Brenda Besemer et al.
Christoph Schultheiß et al.
Viral vectors have successfully modified T cells to express chimeric antigen receptors (CARs), leading to clinical approvals. However, their high cost and regulatory challenges hinder rapid clinical translation. Here, we demonstrate that ou...
Directed evolution of liver-detargeted AAV vectors for systemic gene delivery to skeletal muscle and heart [0.03%]
用于全身基因递送到骨骼肌和心脏的肝去靶向AAV载体的定向进化
Elad Firnberg,Sigmund K S Tejada,Samantha A Yost et al.
Elad Firnberg et al.
Adeno-associated virus (AAV) gene therapies that require systemic administration of high vector doses are associated with hepatotoxicity risk, given the liver tropism of most AAV vectors. We combined screening of natural serotypes, targeted...