rAAV2-Retro Enables Extensive and High-Efficient Transduction of Lower Motor Neurons following Intramuscular Injection
Open accessAbstract
The motor system controls muscle movement through lower motor neurons in the spinal cord and brainstem. Lower motor neurons are efferent neurons in the central nervous system (CNS) characterized by axonal projections that reach specific targets in the periphery. Lower motor neuron lesions result in the denervation and dysfunction of peripheral skeletal muscle. Great progress has been made to develop therapeutic strategies to transduce lower motor neurons with genes. However, the widespread distribution of lower motor neurons makes their specific, extensive, and efficient transduction a challenge. In this study, we demonstrated that, compared to the other tested recombinant adeno-associated virus (rAAV) serotypes, rAAV2-retro mediated the most efficient retrograde transduction of lower motor neurons in the spinal cord following intramuscular injection in neonatal mice. A single injection of rAAV2-retro in a single muscle enabled the efficient and extensive transduction of lower motor neurons in the spinal cord and brainstem rather than transducing only the lower motor neurons connected to the injected muscle. rAAV2-retro achieved the extensive transduction of lower motor neurons by the cerebrospinal fluid pathway. Our work suggests that gene delivery via the intramuscular injection of rAAV2-retro represents a promising tool in the development of gene therapy strategies for motor neuron diseases.
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AAV-mediated gene therapy using IM delivery is minimally invasive in local muscle tissue and undergoes a cascade intracellular event for retrograde axonal trafficking into neuronal soma.
“AAV-mediated gene therapy using IM delivery is minimally invasive in local muscle tissue and undergoes a cascade intracellular event for retrograde axonal trafficking into neuronal soma [99, 100].”
From Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside (2024) · cites this paper as [100]
The Discussion (page unavailable) describes intramuscular administration as minimally invasive and says rAAV can use axonal transport to travel toward lower motor neurons. It does not describe a cascade of intracellular events leading to the neuronal soma; it also reports cerebrospinal-fluid spread as a pathway for the extensive transduction observed in this study. (LLM, conf=0.83)
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Self-citation
- Authors
- Chen, Z., Fan, G., Li, A., Yuan, J., & Xu, T.
- Affiliations
- Wuhan National Laboratory for Optoelectronics (CN)
- Nanchang University (CN)
- Corresponding author
- Yuan, Jing
- Xu, Tonghui
- Venue
- Molecular Therapy - Methods & Clinical Development
- Publisher
- Elsevier BV
- Published
- 2020-06
- Volume
- 17
- Pages
- 21-33
- ISSN
- 2329-0501 (ISSN-L)
- PMC
- PMC6926343
- OpenAlex
- W2989938966
- Cited by
- 41
- References
- 38
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 7 · 2023: 7 · 2022: 7 · 2021: 7 · 2020: 2
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Therapy — Methods & Clinical Development (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Key Laboratory of Jiangxi Province for Persistent Pollutants Control and Resources Recycle (20192BCD40003)
- National Natural Science Foundation of China (81671374, 91632302, 91749209)
- Ministry of Science and Technology of the People's Republic of China
- National Basic Research Program of China (2017YFA0700402)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- lower motor neurons, intramuscular injection, cerebrospinal fluid pathways, spinal cord, brainstem, neonatal mice
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