Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Gene Therapy00:59

Gene Therapy

25.1K
Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be...
25.1K
In-vitro Mutagenesis01:16

In-vitro Mutagenesis

13.7K
To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
13.7K
What is Genetic Engineering?00:49

What is Genetic Engineering?

73.4K
Overview
73.4K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Antineuronal antibody titres in autoimmune encephalitis: clinical implications for diagnosis and long-term immunotherapy.

Frontiers in immunology·2026
Same author

Gene Portals: A Framework for Integrating Clinical, Functional, and Structural Evidence into Rare Disease Variant Classification.

medRxiv : the preprint server for health sciences·2026
Same author

Sleep magnetoencephalography enhances detection and source imaging of seizures and fast oscillations in focal cortical dysplasia.

Epilepsia·2026
Same author

Uncovering targets and molecular pathways for personalizing treatment in epilepsy.

Expert opinion on therapeutic targets·2026
Same author

Comprehensive evaluation of EEG spatial sampling, head modelling and parcellation effects on network alterations in idiopathic generalized epilepsy.

Brain communications·2026
Same author

Ketogenic Diet in Super-Refractory Status Epilepticus: A Retrospective Cohort Study with Severity-Matched Controls in Critically Ill Adults.

Neurocritical care·2026

Related Experiment Video

Updated: May 29, 2025

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
08:22

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations

Published on: December 1, 2017

8.6K

Gene-replacement therapy in neurodevelopmental disorders: progress and challenges.

Holger Lerche1, Ulrike Bs Hedrich1, Thomas V Wuttke1,2

  • 1Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, and.

The Journal of Clinical Investigation
|February 3, 2025
PubMed
Summary

Gene replacement therapy using adeno-associated virus (AAV) shows promise for SLC6A1 gene disorders. Early administration via intrathecal injection in mice is most effective, highlighting the critical role of GABA metabolism in brain development.

More Related Videos

Rapid Detection of Neurodevelopmental Phenotypes in Human Neural Precursor Cells NPCs
10:47

Rapid Detection of Neurodevelopmental Phenotypes in Human Neural Precursor Cells NPCs

Published on: March 2, 2018

9.9K
Transplantation of Human Stem Cell-Derived GABAergic Neurons into the Early Postnatal Mouse Hippocampus to Mitigate Neurodevelopmental Disorders
05:00

Transplantation of Human Stem Cell-Derived GABAergic Neurons into the Early Postnatal Mouse Hippocampus to Mitigate Neurodevelopmental Disorders

Published on: November 11, 2022

2.3K

Related Experiment Videos

Last Updated: May 29, 2025

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
08:22

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations

Published on: December 1, 2017

8.6K
Rapid Detection of Neurodevelopmental Phenotypes in Human Neural Precursor Cells NPCs
10:47

Rapid Detection of Neurodevelopmental Phenotypes in Human Neural Precursor Cells NPCs

Published on: March 2, 2018

9.9K
Transplantation of Human Stem Cell-Derived GABAergic Neurons into the Early Postnatal Mouse Hippocampus to Mitigate Neurodevelopmental Disorders
05:00

Transplantation of Human Stem Cell-Derived GABAergic Neurons into the Early Postnatal Mouse Hippocampus to Mitigate Neurodevelopmental Disorders

Published on: November 11, 2022

2.3K

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Loss-of-function variants in the SLC6A1 gene, encoding the GAT1 GABA transporter, cause severe neurodevelopmental disorders.
  • Gene replacement therapy is a potential treatment strategy for these disorders, requiring precise delivery of therapeutic genes.

Purpose of the Study:

  • To evaluate different strategies for AAV-mediated GAT1 gene replacement in mouse models of SLC6A1 deficiency.
  • To determine optimal promoters, injection methods, and timing for effective gene delivery and therapeutic outcomes.

Main Methods:

  • Adeno-associated virus type 9 (AAV9) vectors with two different promoters were tested.
  • Three injection modalities (intrathecal, intracerebroventricular, intraparenchymal) and various administration timings were assessed.
  • Gene expression, tolerability, and therapeutic efficacy were evaluated in heterozygous and homozygous GAT1 knockout mice.

Main Results:

  • Intrathecal administration of AAV9 vectors at postnatal day 5 resulted in high GAT1 expression and was well-tolerated.
  • Gene replacement therapy was ineffective when administered at later disease stages.
  • Early gene reconstitution is crucial for therapeutic success, underscoring the importance of GABA metabolism during early brain development.

Conclusions:

  • Intrathecal AAV9 delivery at an early developmental stage is a promising strategy for GAT1 gene replacement therapy.
  • The timing of gene therapy is critical, with early intervention being essential for treating SLC6A1-related disorders.
  • These findings emphasize the vital role of GABAergic neurotransmission in early brain development and the potential of gene therapy for related neurodevelopmental conditions.