The DOI matches its Crossref record; 82 of the 82 references it cites were found in a registry or an index.
A NeuroD1 AAV-Based Gene Therapy for Functional Brain Repair after Ischemic Injury through In Vivo Astrocyte-to-Neuron Conversion
Open accessAbstract
Adult mammalian brains have largely lost neuroregeneration capability except for a few niches. Previous studies have converted glial cells into neurons, but the total number of neurons generated is limited and the therapeutic potential is unclear. Here, we demonstrate that NeuroD1-mediated in situ astrocyte-to-neuron conversion can regenerate a large number of functional new neurons after ischemic injury. Specifically, using NeuroD1 adeno-associated virus (AAV)-based gene therapy, we were able to regenerate one third of the total lost neurons caused by ischemic injury and simultaneously protect another one third of injured neurons, leading to a significant neuronal recovery. RNA sequencing and immunostaining confirmed neuronal recovery after cell conversion at both the mRNA level and protein level. Brain slice recordings found that the astrocyte-converted neurons showed robust action potentials and synaptic responses at 2 months after NeuroD1 expression. Anterograde and retrograde tracing revealed long-range axonal projections from astrocyte-converted neurons to their target regions in a time-dependent manner. Behavioral analyses showed a significant improvement of both motor and cognitive functions after cell conversion. Together, these results demonstrate that in vivo cell conversion technology through NeuroD1-based gene therapy can regenerate a large number of functional new neurons to restore lost neuronal functions after injury.
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Revisiting astrocyte to neuron conversion with lineage tracing in vivo
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Self-citationTherapeutic Targeting Strategies for Early- to Late-Staged Alzheimer’s Disease
Kang, Y. J., Diep, Y. N., Tran, M., & Cho, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249591 · Cited by 36
Metadata
- Authors
- Chen, Y.-C., Ma, N.-X., Pei, Z.-F., Wu, Z., Do-Monte, F. H., Keefe, S., Yellin, E., Chen, M. S., Yin, J.-C., Lee, G., Minier-Toribio, A., Hu, Y., Bai, Y.-T., Lee, K., Quirk, G. J., & Chen, G.
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 28
- Issue
- 1
- Pages
- 217-234
- ISSN
- 1525-0016 (ISSN-L)
- OpenAlex
- W2972007441
- Cited by
- 312
- References
- 82
- FWCI
- 11.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Chen, Y.-C., Ma, N.-X., Pei, Z.-F., Wu, Z., Do-Monte, F. H., Keefe, S., Yellin, E., Chen, M. S., Yin, J.-C., Lee, G., Minier-Toribio, A., Hu, Y., Bai, Y.-T., Lee, K., Quirk, G. J., & Chen, G. (2020). A NeuroD1 AAV-Based Gene Therapy for Functional Brain Repair after Ischemic Injury through In Vivo Astrocyte-to-Neuron Conversion. Molecular Therapy. https://doi.org/10.1016/j.ymthe.2019.09.003
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