ORCID Profile
0000-0001-7295-2738
Current Organisations
Universidad del Desarrollo
,
University College London
,
Hospital Clinico de la Universidad de Chile
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Publications
Generation of light-producing somatic-transgenic mice using adeno-associated virus vectors
Publisher: Cold Spring Harbor Laboratory
Date: 22-05-2018
DOI: 10.1101/328310
Abstract: We have previously designed a library of lentiviral vectors to generate somatic-transgenic rodents to monitor signalling pathways in diseased organs using whole-body bioluminescence imaging, in conscious, freely moving rodents. We have now expanded this technology to adeno-associated viral vectors. We first explored bio-distribution by assessing GFP expression after neonatal intravenous delivery of AAV8. We observed widespread gene expression in, central and peripheral nervous system, liver, kidney and skeletal muscle. Next, we selected a constitutive SFFV promoter and NFκB binding sequence for bioluminescence and biosensor evaluation. An intravenous injection of AAV8 containing firefly luciferase and eGFP under transcriptional control of either element resulted in strong and persistent widespread luciferase expression. A single dose of LPS-induced a 10-fold increase in luciferase expression in AAV8-NFκB mice and immunohistochemistry revealed GFP expression in cells of astrocytic and neuronal morphology. Importantly, whole-body bioluminescence persisted up to 240 days. To further restrict biosensor activity to the CNS, we performed intracerebroventricular injection of each vector. We observed greater restriction of bioluminescence to the head and spine with both vectors. Immunohistochemistry revealed strongest expression in cells of neuronal morphology. LPS administration stimulated a 4-fold increase over baseline bioluminescence. We have validated a novel biosensor technology in an AAV system by using an NFκB response element and revealed its potential to monitor signalling pathway in a non-invasive manner using a model of LPS-induced inflammation. This technology employs the 3R’s of biomedical animal research, complements existing germline-transgenic models and may be applicable to other rodent disease models with the use of different response elements.
Age-Related Seroprevalence of Antibodies Against AAV-LK03 in a UK Population Cohort
Publisher: Mary Ann Liebert Inc
Date: 2019
DOI: 10.1089/HUM.2018.098
Gene therapy restores dopamine transporter expression and ameliorates pathology in iPSC and mouse models of infantile parkinsonism
Publisher: American Association for the Advancement of Science (AAAS)
Date: 19-05-2021
DOI: 10.1126/SCITRANSLMED.AAW1564
Abstract: Viral vectors restore dopamine transporter function and ameliorate neuropathology in iPSC-derived neurons and a mouse model of infantile parkinsonism.
Generation of light-producing somatic-transgenic mice using adeno-associated virus vectors
Publisher: Springer Science and Business Media LLC
Date: 07-02-2020
DOI: 10.1038/S41598-020-59075-3
Abstract: We have previously designed a library of lentiviral vectors to generate somatic-transgenic rodents to monitor signalling pathways in diseased organs using whole-body bioluminescence imaging, in conscious, freely moving rodents. We have now expanded this technology to adeno-associated viral vectors. We first explored bio-distribution by assessing GFP expression after neonatal intravenous delivery of AAV8. We observed widespread gene expression in, central and peripheral nervous system, liver, kidney and skeletal muscle. Next, we selected a constitutive SFFV promoter and NFκB binding sequence for bioluminescence and biosensor evaluation. An intravenous injection of AAV8 containing firefly luciferase and eGFP under transcriptional control of either element resulted in strong and persistent widespread luciferase expression. A single dose of LPS-induced a 10-fold increase in luciferase expression in AAV8-NFκB mice and immunohistochemistry revealed GFP expression in cells of astrocytic and neuronal morphology. Importantly, whole-body bioluminescence persisted up to 240 days. We have validated a novel biosensor technology in an AAV system by using an NFκB response element and revealed its potential to monitor signalling pathway in a non-invasive manner in a model of LPS-induced inflammation. This technology complements existing germline-transgenic models and may be applicable to other rodent disease models.
Related Organisations
University College London
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for Juan Antinao Diaz.