Journal Article

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

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

2017

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 59 / 59/78 / 692/308/2056 / 692/308/53/2422 / Aminopeptidases - metabolism / Brain - diagnostic imaging / Capsid Proteins - analysis / Capsid Proteins - radiation effects / Capsids / Clinical trials / CLN2 protein / Dependovirus - genetics / Dipeptidyl-Peptidases and Tripeptidyl-Peptidases - metabolism / Expression vectors / Gene therapy / Gene Transfer Techniques / Genetic Therapy - methods / Genetic Vectors - analysis / Hereditary diseases / Humanities and Social Sciences / Humans / Iodine / Iodine Radioisotopes - administration & dosage / Male / multidisciplinary / Neural coding / Neuronal ceroid lipofuscinosis / Positron emission tomography / Radioiodination / Radionuclide Imaging - methods / Science / Science (multidisciplinary) / Serine Proteases - metabolism / Spatial distribution / Temporal distribution / Tripeptidyl-Peptidase 1 / Tropism / Urea - analogs & derivatives / Urea - pharmacology / Vectors (Biology)