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

Publication Type	Academic Article
Authors	Kothari P, De B, He B, Chen A, Chiuchiolo M, Kim D, Nikolopoulou A, Amor-Coarasa A, Dyke J, Voss H, Kaminsky S, Foley C, Vallabhajosula S, Hu B, DiMagno S, Sondhi D, Crystal R, Babich J, Ballon D
Journal	Sci Rep
Volume	7
Pagination	39594
Date Published	01/06/2017
ISSN	2045-2322
Keywords	Brain, Capsid Proteins, Dependovirus, Gene Transfer Techniques, Genetic Vectors, Iodine Radioisotopes, Radionuclide Imaging
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.
DOI	10.1038/srep39594
PubMed ID	28059103
PubMed Central ID	PMC5216390