Radioiodinated Capsids Facilitate in Vivo Non-Invasive Tracking of Adeno-Associated Gene Transfer Vectors

P. Kothari, B. P. De, B. He, A. Chen, M. J. Chiuchiolo, D. Kim, A. Nikolopoulou, A. Amor-Coarasa, J. P. Dyke, H. U. Voss, S. M. Kaminsky, C. P. Foley, S. Vallabhajosula, B. Hu, S. G. DiMagno, D. Sondhi, Ronald Crystal, J. W. Babich, D. Ballon

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Viral vector mediated gene therapy has become commonplace in clinical trials for a wide range of inherited disorders. Successful gene transfer depends on a number of factors, of which tissue tropism is among the most important. To date, definitive mapping of the spatial and temporal distribution of viral vectors in vivo has generally required postmortem examination of tissue. Here we present two methods for radiolabeling adeno-associated virus (AAV), one of the most commonly used viral vectors for gene therapy trials, and demonstrate their potential usefulness in the development of surrogate markers for vector delivery during the first week after administration. Specifically, we labeled adeno-associated virus serotype 10 expressing the coding sequences for the CLN2 gene implicated in late infantile neuronal ceroid lipofuscinosis with iodine-124. Using direct (Iodogen) and indirect (modified Bolton-Hunter) methods, we observed the vector in the murine brain for up to one week using positron emission tomography. Capsid radioiodination of viral vectors enables non-invasive, whole body, in vivo evaluation of spatial and temporal vector distribution that should inform methods for efficacious gene therapy over a broad range of applications.

Original languageEnglish
Article number39594
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 6 Jan 2017
Externally publishedYes

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Capsid
Genetic Therapy
Dependovirus
Neuronal Ceroid-Lipofuscinoses
Genes
Tropism
Viral Genes
Thromboplastin
Iodine
Positron-Emission Tomography
Autopsy
Biomarkers
Clinical Trials
Brain

ASJC Scopus subject areas

  • General

Cite this

Kothari, P., De, B. P., He, B., Chen, A., Chiuchiolo, M. J., Kim, D., ... Ballon, D. (2017). Radioiodinated Capsids Facilitate in Vivo Non-Invasive Tracking of Adeno-Associated Gene Transfer Vectors. Scientific Reports, 7, [39594]. https://doi.org/10.1038/srep39594

Radioiodinated Capsids Facilitate in Vivo Non-Invasive Tracking of Adeno-Associated Gene Transfer Vectors. / Kothari, P.; De, B. P.; He, B.; Chen, A.; Chiuchiolo, M. J.; Kim, D.; Nikolopoulou, A.; Amor-Coarasa, A.; Dyke, J. P.; Voss, H. U.; Kaminsky, S. M.; Foley, C. P.; Vallabhajosula, S.; Hu, B.; DiMagno, S. G.; Sondhi, D.; Crystal, Ronald; Babich, J. W.; Ballon, D.

In: Scientific Reports, Vol. 7, 39594, 06.01.2017.

Research output: Contribution to journalArticle

Kothari, P, De, BP, He, B, Chen, A, Chiuchiolo, MJ, Kim, D, Nikolopoulou, A, Amor-Coarasa, A, Dyke, JP, Voss, HU, Kaminsky, SM, Foley, CP, Vallabhajosula, S, Hu, B, DiMagno, SG, Sondhi, D, Crystal, R, Babich, JW & Ballon, D 2017, 'Radioiodinated Capsids Facilitate in Vivo Non-Invasive Tracking of Adeno-Associated Gene Transfer Vectors', Scientific Reports, vol. 7, 39594. https://doi.org/10.1038/srep39594
Kothari, P. ; De, B. P. ; He, B. ; Chen, A. ; Chiuchiolo, M. J. ; Kim, D. ; Nikolopoulou, A. ; Amor-Coarasa, A. ; Dyke, J. P. ; Voss, H. U. ; Kaminsky, S. M. ; Foley, C. P. ; Vallabhajosula, S. ; Hu, B. ; DiMagno, S. G. ; Sondhi, D. ; Crystal, Ronald ; Babich, J. W. ; Ballon, D. / Radioiodinated Capsids Facilitate in Vivo Non-Invasive Tracking of Adeno-Associated Gene Transfer Vectors. In: Scientific Reports. 2017 ; Vol. 7.
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