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AAV6 mediated Gsx1 expression in neural stem progenitor cells promotes neurogenesis and restores locomotor function after contusion spinal cord injury.
Finkel, Zachary; Esteban, Fatima; Rodriguez, Brianna; Clifford, Tanner; Joseph, Adelina; Alostaz, Hani; Dalmia, Mridul; Gutierrez, Juan; Tamasi, Matthew J; Zhang, Samuel Ming; Simone, Jonah; Petekci, Hafize; Nath, Susmita; Escott, Miriam; Garg, Shivam Kumar; Gormley, Adam J; Kumar, Suneel; Gulati, Sonia; Cai, Li.
Afiliação
  • Finkel Z; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, NJ 08854, USA.
  • Esteban F; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, NJ 08854, USA.
  • Rodriguez B; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, NJ 08854, USA.
  • Clifford T; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, NJ 08854, USA.
  • Joseph A; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, NJ 08854, USA.
  • Alostaz H; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, NJ 08854, USA.
  • Dalmia M; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, NJ 08854, USA.
  • Gutierrez J; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, NJ 08854, USA; University of California, Santa Barbara, CA 93106, USA.
  • Tamasi MJ; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, NJ 08854, USA.
  • Zhang SM; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, NJ 08854, USA.
  • Simone J; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, NJ 08854, USA.
  • Petekci H; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, NJ 08854, USA.
  • Nath S; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, NJ 08854, USA.
  • Escott M; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, NJ 08854, USA.
  • Garg SK; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, NJ 08854, USA.
  • Gormley AJ; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, NJ 08854, USA.
  • Kumar S; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, NJ 08854, USA.
  • Gulati S; NeuroNovus Therapeutics Inc., 135 E 57th St., New York, NY 10022, USA.
  • Cai L; Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, NJ 08854, USA; NeuroNovus Therapeutics Inc., 135 E 57th St., New York, NY 10022, USA. Electronic address: lcai@rutgers.edu.
Neurotherapeutics ; 21(4): e00362, 2024 Apr 24.
Article em En | MEDLINE | ID: mdl-38664194
ABSTRACT
Genomic screened homeobox 1 (Gsx1 or Gsh1) is a neurogenic transcription factor required for the generation of excitatory and inhibitory interneurons during spinal cord development. In the adult, lentivirus (LV) mediated Gsx1 expression promotes neural regeneration and functional locomotor recovery in a mouse model of lateral hemisection spinal cord injury (SCI). The LV delivery method is clinically unsafe due to insertional mutations to the host DNA. In addition, the most common clinical case of SCI is contusion/compression. In this study, we identify that adeno-associated virus serotype 6 (AAV6) preferentially infects neural stem/progenitor cells (NSPCs) in the injured spinal cord. Using a rat model of contusion SCI, we demonstrate that AAV6 mediated Gsx1 expression promotes neurogenesis, increases the number of neuroblasts/immature neurons, restores excitatory/inhibitory neuron balance and serotonergic neuronal activity through the lesion core, and promotes locomotor functional recovery. Our findings support that AAV6 preferentially targets NSPCs for gene delivery and confirmed Gsx1 efficacy in clinically relevant rat model of contusion SCI.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Neurotherapeutics Assunto da revista: NEUROLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Neurotherapeutics Assunto da revista: NEUROLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos