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Efficient Gene Transfer to the Central Nervous System by Single-Stranded Anc80L65
- Source :
- Molecular Therapy: Methods & Clinical Development, Vol 10, Iss, Pp 197-209 (2018), Molecular Therapy. Methods & Clinical Development
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Adeno-associated viral vectors (AAVs) have demonstrated potential in applications for neurologic disorders, and the discovery that some AAVs can cross the blood-brain barrier (BBB) after intravenous injection has further expanded these opportunities for non-invasive brain delivery. Anc80L65, a novel AAV capsid designed from in silico reconstruction of the viral evolutionary lineage, has previously demonstrated robust transduction capabilities after local delivery in various tissues such as liver, retina, or cochlea, compared with conventional AAVs. Here, we compared the transduction efficacy of Anc80L65 with conventional AAV9 in the CNS after intravenous, intracerebroventricular (i.c.v.), or intraparenchymal injections. Anc80L65 was more potent at targeting the brain and spinal cord after intravenous injection than AAV9, and mostly transduced astrocytes and a wide range of neuronal subpopulations. Although the efficacy of Anc80L65 and AAV9 is similar after direct intraparenchymal injection in the striatum, Anc80L65’s diffusion throughout the CNS was more extensive than AAV9 after i.c.v. infusion, leading to widespread EGFP expression in the cerebellum. These findings demonstrate that Anc80L65 is a highly efficient gene transfer vector for the murine CNS. Systemic injection of Anc80L65 leads to notable expression in the CNS that does not rely on a self-complementary genome. These data warrant further testing in larger animal models.<br />Graphical Abstract
- Subjects :
- Anc80L65
0301 basic medicine
Cerebellum
lcsh:QH426-470
viruses
In silico
Central nervous system
Striatum
Biology
Article
Viral vector
Green fluorescent protein
03 medical and health sciences
Transduction (genetics)
Genetics
medicine
lcsh:QH573-671
Molecular Biology
lcsh:Cytology
AAV
central nervous system
Spinal cord
3. Good health
Cell biology
lcsh:Genetics
030104 developmental biology
medicine.anatomical_structure
adeno-associated
Molecular Medicine
Subjects
Details
- ISSN :
- 23290501
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Molecular Therapy - Methods & Clinical Development
- Accession number :
- edsair.doi.dedup.....9401173ae6b9ef26e9d2b84a31b3c4bc