Viromics - Shortcut to Functional Genomics

The term "viromics" was introduced on a biochemical pharmacology discussion conference in 2001 (Lotze MT and Kost TA. Cancer Gene Therapy. 2002 Aug; 9(8):692-9). It refers to "the use of viruses and viral gene transfer to explore the complexity arising from the vast array of new targets available from the human and murine genomes". 

In deed, among the >30,000 human genes identified, only a small portion have known functions. It is critical to investigate and validate functions of unknown genes, to further expand the pool of "druggable" targets. To successfully conduct this job, genes of interest ought to be introduced into model systems for phenotypic characterization. Such model systems can be cultured cell line, primary culture, or animal disease models. 

Viral vectors have been proven to be the most efficient in gene delivery, leading to more than 30,000 publications since 1990. The extensive use of viral vector techniques has become an expressway to the target of functional genomics.

Many viral vector systems have been developed over time and adenovirus, adeno-associated virus (AAV), and retrovirus become widely used. Among the 1000 gene therapy clinical trails worldwide, more than 55% use these three type of vectors (www.wiley.co.uk/genmed/clinical/). The reasons for their popularity are as below:

1) Better understanding of the virology. These viral systems are well studied. Significant amount of knowledge on the viral life cycle as well as viral protein functions are accumulated during academic research. This information allows construction of recombinant viral vector to hold non-viral genes for delivery, as well as complimentary systems to produce the recombinant (usually defective) virus.  

2) Established application in gene delivery. Again, cumulative data on the use of these viral vectors in gene delivery to various cells and tissues help other researchers to make their choices. People need to know the vector tropism, infection efficiency, immune response, and potential toxicity before designing their own experiments.

3) Significant advantage in performance. Practical reasons such as ease of construction, good production titer, high transgene expression, and high safety profiles determine the application potential of the viral vectors. Adenovirus, AAV, and retrovirus are the most commonly used viral systems due to the established protocol, excellent performance in gene transduction, and relatively safe to use in standard lab setting.

Gene Delivery Techniques

So what kind of methods are out there for gene delivery?

For in vitro studies, plasmid transfection is commonly used. It is easy to perform, fast, and can be used for transient expression or generating stable cell lines. However, this non-viral based method has highly variable efficiency depending on cell types. Most of the time <10% of the cells can be transfected even with the powerful lipid-based DNA complex. Also, the efficiency for establishing genome- integrated, stable cell line is much lower (<0.01%). 

The biggest advantage of using viral vectors for in vitro studies is high efficiency. Viral vectors can infect 100% of the cells at the adequate titer. Adeno, AAV, and retroviruses all have very broad tropism, and are capable of infecting all kind of cells with high efficiency. When your study requires the whole cell population to be transduced (such as gene down-regulation by RNAi), or your work involves some "difficult" cell lines which are refractory to plasmid transfection, viral vectors are your best choice.

In vivo gene delivery is dominated by viral vector approaches. Viral vectors can delivered by intravenous infusion or local injection. Since viral infection is receptor mediated, tissue specificity of viral vectors can be achieved by its specific tropism, through pseudotyping, or capsid modification. The use of tissue specific promoters also help to limit the recombinant gene expression in target tissues. The high efficiency in gene delivery makes possible both in vivo gene function research as well as gene therapy studies for certain diseases.

With many different viral vectors systems available, researchers can make the best choice based on the inherent properties of each system for their particular applications. Listed below are brief comparison of features in different gene delivery systems. Please refer to our Technology Section for more detail.

Unmet Needs

Viral vectors clearly have advantages in gene function studies. However, many technical issues prevent this method from revealing its full potential. The following technical challenges are the most significant:

1. Virological experience is required for successful viral production. Now many researchers use do-it-yourself kits for recombinant viral production.  However, people find it still very frustrating if you are new to virology since the technical support from those kit venders are not adequate. 

2. Viral production is time-consuming and involves extensive lab work. One study may need multiple viral vectors to be made, and the work load is prohibitive. This could be a major reason many researchers hesitate using viral vectors. Usually viral vectors are just research tools in your project. You may end up spending a lot of time making those "tools" and not on the true scientific issues. 

3. Inconsistency in viral vector quality renders experimental results hard to interpret. This is mainly due to lack of experience in viral production. Again it is an issue of time/effort, i.e., whether you want to set up complicated assays to check on your vectors. 

The mission of Applied Viromics is to better address these unmet needs. With Applied Viromics to take care of all the issues above, you can better enjoy the power of viral vector tools in gene delivery. We offer pre-made viral vectors, or custom-made vectors on your demand. We provide extensive analysis to ensure the highest quality of your vectors, and you will not need to spend any of your time and manpower on them.