Gene Therapy Vector Targeting Evaluation Service
Advancements in technology which enable precise targeting of cells by viral vectors have increased the likelihood of developing gene therapies for orphan diseases. We provide our clients with advanced assessments of targeting capabilities as well as biodistribution studies of viral vectors with model systems and imaging technologies.
Background
In gene therapy, the biggest hurdle is delivering the therapeutic transgene to the right tissue, which can now be done with ease using Targetable vectors. There is a multitude of approaches for various viruses (and their derivative vectors) that seek to insert a nucleic acid package into target cells. After completing primary proof tests and constructing the vector, it is critical to assess the functionalities of the targeting strategy using them, no matter what targeting strategy was employed. This piece of information is highly valuable in terms of improving gene therapy.
To assess novel targeting approaches during the preclinical phase for new therapies aimed at rare diseases, we created and validated several primary cells, tissue explant systems, and transgenic animal models that mimic the human condition to varying degrees. In addition, the application of imaging technologies for vector targeting evaluation is very encouraging as it provides the possibility of monitoring the vectors in real time in vivo without the need for sacrificing animal models.
Fig. 1 Tracking of adenovirus infection in cultured cancer cells. (Le L P, et al., 2006)
Our Services
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 focus in imaging construction is the application of radioactive and light-emitting systems. The technologies in aid include positron emission tomography (PET) and magnetic resonance imaging (MRI).
Years of intensive research work combined with many years of service in directing the efforts in the developing gene therapy viral vectors, our firm offers our clients the determination of the key elements such as titer, assayed for the capsid content and other aggregation, and also for determination of the targeting efficiency. Our team of highly specialized researchers work to solve the numerous problems associated with the development of gene therapy medicinal forms. If you need our services, please feel free to contact us for more details.
Reference
- 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.