A brief review of reporter gene imaging in oncolytic virotherapy and gene therapy

Abstract

Reporter gene imaging (RGI) can accelerate development timelines for gene and viral therapies by facilitating rapid and noninvasive in vivo studies to determine the biodistribution, magnitude, and durability of viral gene expression and/or virus infection. Functional molecular imaging systems used for this purpose can be divided broadly into deep-tissue and optical modalities. Deep-tissue modalities, which can be used in animals of any size as well as in human subjects, encompass single photon emission computed tomography (SPECT), positron emission tomography (PET), and functional/molecular magnetic resonance imaging (f/mMRI). Optical modalities encompass fluorescence, bioluminescence, Cerenkov luminescence, and photoacoustic imaging and are suitable only for small animal imaging. Here we discuss the mechanisms of action and relative merits of currently available reporter gene systems, highlighting the strengths and weaknesses of deep tissue versus optical imaging systems and the hardware/reagents that are used for data capture and processing. In light of recent technological advances, falling costs of imaging instruments, better availability of novel radioactive and optical tracers, and a growing realization that RGI can give invaluable insights across the entire in vivo translational spectrum, the approach is becoming increasingly essential to facilitate the competitive development of new virus- and gene-based drugs.

Senecavirus A as an Oncolytic Virus: Prospects, Challenges and Development Directions

“…These provide new ways for the diagnosis and treatment of tumors in the future ( 96 ). At present, viral molecular imaging technologies are mainly divided into two categories: optical imaging and deep tissue imaging ( 96 , 97 ) ( Figure 3D ). The principle relies on the integration of a reporter gene into the OV genome, allowing it to be monitored in the host upon translation.…”

“…The principle relies on the integration of a reporter gene into the OV genome, allowing it to be monitored in the host upon translation. Ultimately, an external device is used to track these proteins to complete the imaging ( 97 ).…”

“…Optical imaging methods mainly include Fluorescence imaging (FI), Bioluminescence imaging (BLI), Cerenkov luminescence imaging (CLI), and Photoacoustic imaging (PAI) ( 97 ). At present, in the research of SVA, the use of optical imaging occupies the dominant position.…”

The Evolution and Future of Targeted Cancer Therapy: From Nanoparticles, Oncolytic Viruses, and Oncolytic Bacteria to the Treatment of Solid Tumors

“…Early detection of tumors can be directly correlated to patient outcomes, and thus represents a pivotal aspect of oncology that should not be ignored. Viral therapy can improve detection thresholds of these scans by engineering them with prodrug converting enzymes [130], receptors [131,132], or symporter/transporters [75,133] to facilitate deep tissue imaging [134]. The luciferase reporter gene in combination with the human Na+/I-symporter (hNIS) gene encoding sodium iodide symporter (NIS) has demonstrated transport of several other radioactive anions in addition to iodine, increasing the sensitivity of SPECT and PET imaging [135,136].…”

“…The luciferase reporter gene in combination with the human Na+/I-symporter (hNIS) gene encoding sodium iodide symporter (NIS) has demonstrated transport of several other radioactive anions in addition to iodine, increasing the sensitivity of SPECT and PET imaging [135,136]. To date, oncolytic viruses have been engineered to express NIS with varying degrees of success [137][138][139][140][141][142][143], largely due to the challenge of increasing viral propagation to overcome the minimum threshold for detection [134,144]. Several theories have been proposed to understand this challenge, with emerging data indicating the TME can modulate NIS expression [133].…”