1.682 hasil
Menampilkan 1–20 · 0,16 detik · RSS
Molecular Therapy: Methods & Clinical Development
ISSN 2329-0501 · Elsevier · 1.682 artikel di indeks
-
Artikel Jurnal
Development of cell lines with increased susceptibility to diverse adeno-associated viral vectors to enable in vitro potency assays
Vectors based on adeno-associated viruses (AAVs) are promising therapeutic modalities used in gene therapy. Robust cell-based assays that demonstrate and quantify the potency of AAV vectors in expressing their transgene are needed for clinical development. However, many AAV clinical serotypes…
-
Artikel Jurnal
CAR T cell engineering impacts antigen-independent activation and co-inhibition
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 our lentivirally (LV) manufactured R110-CAR T cells…
-
Artikel Jurnal
Design of cationic ionizable lipids for the delivery of therapeutic nucleic acids
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-generation RNA medicines, the rational design of next-generation…
-
Artikel Jurnal
In vivo delivery of a fluorogenic antisense oligonucleotide into human leukocytes in a humanized mouse model system
Development of oligonucleotide-based therapeutics has been limited by the lack of effective in vivo delivery vehicles. We previously showed that the presence of an H-type excitonic dimer formed by the covalent binding of two fluorophores with significant transition dipoles on opposite ends of…
-
Artikel Jurnal
Characterization of adeno-associated viral transduction of retinal ganglion cells in adult and old mice
Adeno-associated viral (AAV) vectors are being used increasingly in developing treatments for age-related ocular diseases, including those impacting retinal ganglion cells (RGCs), the output neurons of the eye. However, the effects of persistent transgene expression on RGC structure and function…
-
Artikel Jurnal
Genome-replicating HC-AdV: A novel high-capacity adenoviral vector class featuring enhanced in situ payload expression
High-capacity adenoviral (HC-AdV) vectors offer large transgene capacities and long-term expression of therapeutics but require high doses due to limited transgene expression. In contrast, replication-competent AdV (RC-AdV) vectors enhance in situ transgene expression by genome replication and…
-
Artikel Jurnal
Biodistribution of AAV1, AAV5, AAV9, and AAVDJ serotypes after intra-cisterna magna delivery in non-human primates
Delivering drugs effectively to the central nervous system (CNS) is a major challenge in drug development, including adeno-associated virus (AAV) gene therapy. The cerebrospinal fluid (CSF) circulates through the ventricular system and the subarachnoid space, surrounding both the brain and spinal…
-
Artikel Jurnal
High-potency MyoAAV capsids enhanced skeletal muscle correction in a mouse model of GSD IIIa
Glycogen storage disease type IIIa (GSD IIIa) affects multiple tissues, including liver, heart, and skeletal muscles. We recently reported that an adeno-associated virus serotype 9 vector expressing pullulanase, a bacterial glycogen debranching enzyme, driven by an immunotolerizing dual promoter…
-
Artikel Jurnal
AAV hamartin gene therapy in a stochastic, cerebral mouse model of tuberous sclerosis type 1
Tuberous sclerosis complex (TSC) is a dominantly inherited disease in which most individuals are born with one defective allele encoding for either hamartin (TSC1) or tuberin (TSC2), with a somatic loss of the other allele leading to abnormal neurodevelopment and upregulation of cell growth in…
-
Artikel Jurnal
GroβT rapidly and reliably mobilizes primitive hematopoietic stem and progenitor cells in nonhuman primates
Autologous hematopoietic stem cell (HSC) gene therapy has gone through remarkable advancements in recent years, especially for the treatment of sickle cell disease (SCD). However, the collection of HSCs from SCD patients requires unique considerations, as granulocyte colony-stimulating factor…
-
Artikel Jurnal
Hematopoietic stem cell gene therapy for the treatment of X-linked agammaglobulinemia
X-linked agammaglobulinemia (XLA) is a rare inborn error of immunity caused by loss-of-function mutations in the gene encoding Bruton’s tyrosine kinase (BTK). XLA patients lack mature B cells and have negligible antibody levels, leaving them susceptible to recurrent bacterial and chronic viral…
-
Artikel Jurnal
Development and implementation of an LC-MS-based multi-attribute method for adeno-associated virus
The multi-attribute method (MAM), a mass spectrometry technique for quantifying amino acid modifications at the peptide level, is becoming a prominent analytical tool in the development of biotherapeutics. The method has promise for adeno-associated virus (AAV) therapeutics, where capsid protein…
-
Artikel Jurnal
Development of LC-MS methods for AAV capsid protein quantification and host cell protein profiling
Accurate quantification and characterization of recombinant adeno-associated virus (rAAV) capsid proteins are critical for evaluating product quality and safety, ensuring batch consistency, and informing process development of their manufacture. The capsid consists of three proteins derived from…
-
Artikel Jurnal
AAV-mediated peripheral scFv's administration to reduce cerebral tau in adult P301S transgenic mice: Mono-vs. combination therapy
Tau is a primary target for immunotherapy in Alzheimer’s disease (AD). Recent studies have shown the potential of anti-tau fragment antibodies in lowering pathological tau levels in vitro and in vivo. Here, we compared the effects of single-chain variable fragments (scFvs) derived from the…
-
Artikel Jurnal
Reversing PAI-1 deficiency in blood using mRNA lipid nanoparticles
Plasminogen activator inhibitor-1 (PAI-1) deficiency is a rare disorder that causes moderate to severe bleeding and cardiac fibrosis, caused by mutation in the SERPINE-1 gene and no detectable circulating PAI-1 protein. There are currently no therapies that can effectively replace PAI-1 because the…
-
Artikel Jurnal
Effects of CRISPR-Cas9-mediated FOXP3 knockout on CAR T cell potency
Persistent antigen stimulation and inflammatory environments drive exhaustion, senescence, and activation-induced cell death, impairing both endogenous and therapeutic T cells. Understanding the mechanisms underlying T cell dysfunction is critical for improving immunotherapies. While the…
-
Artikel Jurnal
Nanoparticle delivery of AMPK activator 991 prevents its toxicity and improves muscle homeostasis in Duchenne muscular dystrophy
Muscular dystrophies, such as Duchenne muscular dystrophy (DMD), are caused by permanent muscle injuries leading to chronic inflammation, with macrophages harboring an altered inflammatory profile contributing to fibrosis through the secretion of transforming growth factor β1 (TGF-β1). We…
-
Artikel Jurnal
HLA-A2 CAR/IL-2-CISC engineered Treg display robust in vitro and in vivo antigen-specific regulatory function
Chimeric antigen (Ag) receptor-expressing T regulatory cells (CAR-Treg) offer therapeutic potential for treating autoimmunity, allograft rejection, and graft-versus-host disease (GvHD). HLA-A∗02 (A2) CAR (A2CAR)-expressing natural Treg have shown efficacy in preclinical models and are being…
-
Artikel Jurnal
Perineural delivery of AAV2/9 in non-human primates is a safe and efficient route for gene therapy in Charcot-Marie-Tooth diseases
AAV-based gene therapy represents an attractive treatment for hereditary peripheral neuropathies Charcot-Marie-Tooth diseases. We recently showed that AAV2/9 vector-expressing GFP, locally injected into mouse and rat sciatic nerves, transduced a large amount of myelinating Schwann cells (mSCs). The…
Menampilkan maksimal 50 halaman. Persempit pencarian dengan filter untuk hasil yang lebih spesifik.