Dosing and Re-Administration of Lentiviral Vector for In Vivo Gene Therapy in Rhesus Monkeys and ADA-Deficient Mice

Denise A. Carbonaro-Sarracino, Alice F. Tarantal, C. Chang I. Lee, Michael L. Kaufman, Stephen Wandro, Xiangyang Jin, Michele Martinez, Danielle N. Clark, Krista Chun, Colin Koziol, Cinnamon L. Hardee, Xiaoyan Wang, Donald B. Kohn

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Adenosine deaminase (ADA)-deficient mice and healthy rhesus monkeys were studied to determine the impact of age at treatment, vector dosage, dosing schedule, repeat administration, biodistribution, and immunogenicity after systemic delivery of lentiviral vectors (LVs). In Ada−/− mice, neonatal treatment resulted in broad vector marking across all tissues analyzed, whereas adult treatment resulted in marking restricted to the liver, spleen, and bone marrow. Intravenous administration to infant rhesus monkeys also resulted in dose-dependent marking in the liver, spleen, and bone marrow. Using an ELISA to monitor anti-vector antibody development, Ada−/− neonatal mice did not produce an antibody response, whereas Ada−/− adult mice produced a strong antibody response to vector administration. In mice and monkeys with repeat administration of LV, a strong anti-vector antibody response was shown in response to the second LV administration, which resulted in LV inactivation. Three separate doses administered to immune competent mice resulted in acute toxicity. Pegylation of the vesicular stomatitis virus G protein (VSV-G)-enveloped LVs showed a less robust anti-vector response but did not prevent the inactivation of the second LV administration. These studies identify important factors to consider related to age and timing of administration when implementing systemic delivery of LVs as a potential therapeutic agent.

Original languageEnglish (US)
Pages (from-to)78-93
Number of pages16
JournalMolecular Therapy - Methods and Clinical Development
StatePublished - Mar 13 2020


  • ADA-deficiency
  • ERT
  • gene therapy
  • immune response
  • in vivo
  • lentiviral vector
  • repeat administration
  • rhesus monkeys

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics


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