Gene Therapy Vector Targeting Evaluation Service
The advent of techniques to target viral vectors to specific cells has greatly improved the chances of successfully developing gene therapies for rare diseases. Our company is committed to providing customers with the assessment of the targeting capabilities and biodistribution analysis of viral vectors through model systems and imaging technologies.
Targetable vectors have shown great promise in the field of gene therapy, allowing accurate and effective delivery of therapeutic transgenes to any pre-selected tissue or cell type in vivo, without affecting neighboring non-target cells. A variety of strategies have been developed for different viruses (and their derivative vectors) to introduce their nucleic acid payload into target cells. Regardless of the targeting strategy used, there is a need to evaluate their targeting capabilities after initial proof studies and vector construction are complete, providing valuable information for optimizing gene therapy.
In order to evaluate new targeting strategies in preclinical drug development for rare diseases, we have developed several models that reflect the human condition to varying degrees including primary cells, tissue explants systems, and transgenic animals. In addition to this, the use of imaging technologies for vector targeting assessment appears particularly promising, offering the ability to monitor vectors in vivo in real time without sacrificing animal models.
Fig. 1 Tracking of adenovirus infection in cultured cancer cells. (Le L P, et al., 2006)
Evaluation of Vector Targeting by Model Systems
- Evaluation of vector targeting by cell-culture systems
The first step in assessing the targeting ability of a viral vector is usually testing in cell lines. We offer a variety of three-dimensional cell culture models including fibroblasts, endothelial cells, immunoreceptor cells, and extracellular matrix to assess the targeting of viral vectors and the possible toxic effects on stromal cells.
- Evaluation of vector targeting by tissue explants
We use tissue-slice systems to obtain detailed information on target and non-target tissue transduction to assess the targeting of viral vectors to any tissue. We have successfully applied this system to analyze targeted adenoviral vector transduction of breast tumors, hepatocytes, and dendritic cells.
- Evaluation of vector targeting by animal models
We are developing immunocompetent transgenic mouse models that express human receptors in a similar expression pattern to humans to evaluate viral vector targeting.
Evaluation of Vector Targeting by Imaging Technologies
We help our customers measure the biodistribution of target vectors in real time with technologies allowing imaging of the distribution of viral vectors in vivo. We develop vectors with novel modalities that allow in vivo imaging through two strategies:
- Attaching the imaging moieties to the vector by genetic fusion to the capsid protein.
- Expressing the imaging moieties in the form of a reporter transgene derived from the viral genome.
Our gene-based imaging utilizes primarily radioactive systems and light-emitting systems. The imaging technologies we offer include positron emission tomography (PET) imaging and magnetic resonance imaging (MRI).
With many years of research and service experience in the field of development of gene therapy viral vectors, our company not only provides customers with the characterization of key attributes such as titer, capsid content, and aggregation but also assessment of the targeting of viral vectors. Our highly qualified research team works to address the many challenges faced in the production of gene therapy formulations. If you need our services, please feel free to contact us for more details.
- Le, L. P.; et al. Dynamic monitoring of oncolytic adenovirus in vivo by genetic capsid labeling. Journal of the National Cancer Institute, 2006, 98(3): 203-214.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.