Old Methods for a New Therapy — Imaging Gene Delivery

The promise of gene based therapies is stronger than ever.  Testament to this is the strides being taken in several areas; including mRNA based delivery and RNA interference.1

These successes are driving “new” applications for an “old” in vivo imaging assay, bioluminescence imaging (BLI).  BLI is based on detection of a reporter gene/protein (traditionally firefly luciferase, FFluc) and has been used most commonly to detect tumor cells engineered to express the reporter.  It is a natural extension to use BLI for imaging gene delivery in vivo, utilizing reporters like FFluc as “tool genes” to assess the delivery platform.2,3

Recent advances to commercialize luciferase reporters that generate light on distinguishable wavelengths have made the assay even more powerful4 (see figure below).  These include renilla, gaussia, vargulin and several other derivatives.  With state of the art imaging instrumentation, resolution of multiple genes/reporters can be achieved longitudinally in the same living subjects = increased information from each animal, and each study.4

At Covance, we are leveraging our long history as the first CRO to be licensed to perform BLI (over a decade ago) to offer multi-spectral in vivo imaging of gene delivery (see figure above).  Please contact us to review examples and discuss potential study designs.

Written by: Patrick McConville, PhD

1“Expression of therapeutic proteins after delivery of chemically modified mRNA in mice,” Nat Biotechnol. (2011) Feb;29(2):154-7. doi: 10.1038/nbt.1733. Epub 2011 Jan 9.
2“Molecular imaging of biological gene delivery vehicles for targeted cancer therapy: beyond viral vectors,” Nucl Med Mol Imaging. (2010) Apr; 44(1): 15-24.
3“Multimodality Imaging of RNA Interference,” Curr Med Chem. (2013) ; 20(29): 3664-3675.
4“Triple Bioluminescence Imaging for In Vivo Monitoring of Cellular Processes,” Molecular Therapy—Nucleic Acids (2013) 2, e99.