Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Intrathecal sc-AAV9-CB-GFP: Systemic Distribution Predominates Following Single-Dose Administration in Cynomolgus Macaques

View ORCID ProfileEmily K. Meseck, Ghiabe Guibinga, Stephen Wang, Cameron McElroy, Eloise Hudry, Keith Mansfield
doi: https://doi.org/10.1101/2021.11.28.470258
Emily K. Meseck
1Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Emily K. Meseck
  • For correspondence: emily.meseck@novartis.com
Ghiabe Guibinga
2Novartis Institutes for BioMedical Research Biologics Center, San Diego, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephen Wang
3Novartis Institutes for BioMedical Research, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cameron McElroy
1Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eloise Hudry
3Novartis Institutes for BioMedical Research, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Keith Mansfield
3Novartis Institutes for BioMedical Research, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

Biodistribution of self-complementary adeno-associated virus-9 (scAAV9)–chicken β promoter–green fluorescent protein (GFP) was assessed in juvenile cynomolgus macaques infused intrathecally via lumbar puncture or the intracisterna magna (1.0×1013 or 3.0×1013 vg/animal), with necropsy 28 days later. Our results characterized central nervous system biodistribution compared with systemic organs/tissues by droplet digital polymerase chain reaction for DNA and in situ hybridization. GFP expression was characterized by Meso Scale Discovery electrochemiluminescence immunosorbent assay and immunohistochemistry (IHC). Biodistribution was widespread but variable, with vector DNA and GFP expression greatest in the spinal cord, dorsal root ganglia (DRG), and certain systemic tissues (e.g., liver), with low concentrations in many brain regions despite direct cerebrospinal fluid administration. Transduction and expression were observed primarily in perivascular astrocytes in the brain, with a paucity in neurons. Greater GFP expression was observed in hepatocytes, striated myocytes, cardiomyocytes, spinal cord lower motor neurons, and DRG sensory neurons by IHC. These results suggest caution for use of scAAV9-based intrathecal delivery with the current expression cassette as a modality for neurologic diseases that require widespread brain neuronal expression. This capsid/expression cassette combination may be better suited for diseases that express a secreted protein and/or do not require widespread brain neuronal transduction.

Competing Interest Statement

Emily K. Meseck and Cameron McElroy are employees of Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Ghiabe Guibinga is an employee of Novartis Institutes for BioMedical Research Biologics Center, San Diego, CA, USA. Stephen Wang, Eloise Hudry, and Keith Mansfield are employees of Novartis Institutes for BioMedical Research, Cambridge, MA, USA.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted November 28, 2021.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Intrathecal sc-AAV9-CB-GFP: Systemic Distribution Predominates Following Single-Dose Administration in Cynomolgus Macaques
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Intrathecal sc-AAV9-CB-GFP: Systemic Distribution Predominates Following Single-Dose Administration in Cynomolgus Macaques
Emily K. Meseck, Ghiabe Guibinga, Stephen Wang, Cameron McElroy, Eloise Hudry, Keith Mansfield
bioRxiv 2021.11.28.470258; doi: https://doi.org/10.1101/2021.11.28.470258
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Intrathecal sc-AAV9-CB-GFP: Systemic Distribution Predominates Following Single-Dose Administration in Cynomolgus Macaques
Emily K. Meseck, Ghiabe Guibinga, Stephen Wang, Cameron McElroy, Eloise Hudry, Keith Mansfield
bioRxiv 2021.11.28.470258; doi: https://doi.org/10.1101/2021.11.28.470258

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Pharmacology and Toxicology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4672)
  • Biochemistry (10333)
  • Bioengineering (7654)
  • Bioinformatics (26281)
  • Biophysics (13497)
  • Cancer Biology (10663)
  • Cell Biology (15392)
  • Clinical Trials (138)
  • Developmental Biology (8485)
  • Ecology (12802)
  • Epidemiology (2067)
  • Evolutionary Biology (16818)
  • Genetics (11380)
  • Genomics (15453)
  • Immunology (10592)
  • Microbiology (25151)
  • Molecular Biology (10193)
  • Neuroscience (54373)
  • Paleontology (399)
  • Pathology (1663)
  • Pharmacology and Toxicology (2889)
  • Physiology (4332)
  • Plant Biology (9223)
  • Scientific Communication and Education (1585)
  • Synthetic Biology (2552)
  • Systems Biology (6769)
  • Zoology (1459)