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A sustained-release gel alleviates neuropathic pain in SNI mice by reversing Glu/GABA imbalance and chloride efflux disorders.
Int J Biol Macromol
January 2025
Department of Pain, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China. Electronic address:
Impaired spinal GABAergic inhibitory neuronal system is one popular target for developing new drugs or procedures for treatment of neuropathic pain, but effective and transferable methods are still lacking. We designed an assembled, temperature sensitive and sustained releasing hydrogel to repair the impaired GABAergic neural system by reversing imbalance of glutamic acid (Glu) and γ-aminobutyric acid (GABA) and healing impaired Cl extrusion capacity of neurons. Hydrogel solution is a mixture of pluronic F-127, recombinant glutamate decarboxylase 67 (rGAD67) protein and CLP257, a K-Cl cotransporter isoform 2 (KCC2) enhancer.
View Article and Find Full Text PDFCharacterization of the function of Adenovirus L4 gene products and their impact on AAV vector production.
Mol Ther Methods Clin Dev
December 2024
Genomic Medicine Unit CMC, Global CMC Development, Sanofi R&D, 225 2nd Avenue, Waltham, MA 02451, USA.
Efficient manufacturing of recombinant adenovirus-associated virus (AAV) vectors is critical to the successful development of genomic medicines. We attempted to optimize AAV vector production in a producer cell line platform. In this system, helper functions required for AAV replication and production are provided via infection with a replication-competent wild-type Adenovirus.
View Article and Find Full Text PDFSelf-Replicating Alphaviruses: From Pathogens to Therapeutic Agents.
Viruses
November 2024
PanTherapeutics, CH1095 Lutry, Switzerland.
Alphaviruses are known for being model viruses for studying cellular functions related to viral infections but also for causing epidemics in different parts of the world. More recently, alphavirus-based expression systems have demonstrated efficacy as vaccines against infectious diseases and as therapeutic applications for different cancers. Point mutations in the non-structural alphaviral replicase genes have generated enhanced transgene expression and created temperature-sensitive expression vectors.
View Article and Find Full Text PDFHydrogels are extensively employed in healthcare due to their adaptable structures, high water content, and biocompatibility, with FDA-approved applications ranging from spinal cord regeneration to local therapeutic delivery. However, clinical hydrogels encounter challenges related to inconsistent therapeutic exposure, unmodifiable release windows, and difficulties in subsurface polymer insertion. Addressing these issues, we engineered injectable, biocompatible hydrogels as a local therapeutic depot, utilizing poly(ethylene glycol) (PEG)-based hydrogels functionalized with bioorthogonal SPAAC handles for network polymerization and functionalization.
View Article and Find Full Text PDFA temperature-sensitive and less immunogenic Sendai virus for efficient gene editing.
J Virol
December 2024
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Unlabelled: The therapeutic potential of gene editing technologies hinges on the development of safe and effective delivery methods. In this study, we developed a temperature-sensitive and less immunogenic Sendai virus (ts SeV) as a novel delivery vector for CRISPR-Cas9 and for efficient gene editing in sensitive human cell types with limited induction of an innate immune response. ts SeV demonstrates high transduction efficiency in human CD34 hematopoietic stem and progenitor cells (HSPCs) including transduction of the CD34/CD38/CD45RA/CD90(Thy1)/CD49f stem cell enriched subpopulation.
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