Improved Noninvasive In Vivo Tracking of AAV-9 Gene Therapy Using the Perchlorate-Resistant Sodium Iodide Symporter from Minke Whale.

• 影响指数: 12.91
• 发表时间: 01 2021 6
• 来源期刊: Mol Ther
• DOI: 10.1016/j.ymthe.2020.09.036
• PMID: 33038323
• 文章类型: Journal Article
• 中科院分区: Q1
• 方向: 生物
• 作者列表: Concilio SC,Suksanpaisan L,Pham L,Peng KW,Russell SJ

关键词: AAV-9; NIS; PET; SLC5A5; SPECT; gene therapy; imaging; perchlorate; sodium iodide symporter

Mesh: Animals; Dependovirus / genetics; Gene Expression; Gene Transfer Techniques; Genes, Reporter; Genetic Vectors / administration & dosage genetics; Mice; Minke Whale; Perchlorates; Positron-Emission Tomography; Symporters / genetics; Tissue Distribution; Tomography, Emission-Computed, Single-Photon

Abstract

The sodium iodide symporter (NIS) is widely used as a reporter gene to noninvasively monitor the biodistribution and durability of vector-mediated gene expression via gamma scintigraphy, single-photon emission computed tomography (SPECT), and positron-emission tomography (PET). However, the approach is limited by background signal due to radiotracer uptake by endogenous NIS-expressing tissues. In this study, using the SPECT tracer pertechnetate (99mTcO4) and the PET tracer tetrafluoroborate (B18F4), in combination with the NIS inhibitor perchlorate, we compared the transport properties of human NIS and minke whale (Balaenoptera acutorostrata scammoni) NIS in vitro and in vivo. Based on its relative resistance to perchlorate, the NIS protein from minke whale appeared to be the superior candidate reporter gene. SPECT and PET imaging studies in nude mice challenged with NIS-encoding adeno-associated virus (AAV)-9 vectors confirmed that minke whale NIS, in contrast to human and endogenous mouse NIS, continues to function as a reliable reporter even when background radiotracer uptake by endogenous NIS is blocked by perchlorate.