Imaging of viruses and transgenes

Gene therapy provides methods to treat the genetic reasons underlying behind the diseases with efficient methods and effect a cure instead of merely relieving the symptoms. After the initial discoveries and clinical trials, extensive research and development has been taken place to chart the full clinical and commercial possibilities of gene therapy.

As there has been success with treating some diseases, there has also been acknowledgement of the boundaries in the knowledge concerning the complex mechanisms in a living body. Some of the drawbacks have raised concern to design novel gene delivery vehicles for safer and more efficient treatments for gene therapy.

During evolution viruses have developed elaborate mechanisms to penetrate cells and take over the cellular machinery, each virus developing its preferred cell type and transduction mechanisms. For gene delivery use, the viral vectors are extensively modified for increased safety and selective transduction of target cells.

An essential part of gene therapy research is the determination of the treatment efficacy by using different methods of analysis. A part of patient safety assesments includes imaging of viral particle biodistribution and transgene efficiency. The following list includes some techniques used for imaging:

• MRI, magnetic resonance imaging (Utilized first time to image viral particle biodistribution: Räty et al 2006)
• PET, positron emission tomography (For imaging HSV1-tk expression)
• SPECT, single photon computer tomography (For imaging receptors or viral particle biodistribution: Raty et al 2007)
• Optical methods (Very sensitive for variation of expression levels)
• Ultrasound imaging (Imaging of various liposomes or microbubbles in vasculature)
• Fluorescence- and light microscopy (Analysis from tissue samples)

More information about gene therapy imaging can be found from here.

Image 1. Viral particles imaged with MRI from rat brain (Räty et al 2006).

a) Iron oxide labelled viruses are accumulated to cells producing cerebrospinal fluid and are visible as dark spot during various time points.

b) The control does not show any signal, as expected.

Gene Therapy Imaging by Jani Räty. Published in the Gene Therapy Review.