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What are Viral Vectors?

Regardless of their origin and family, viruses have evolved elegant strategies to reach and enter specific target cells where they seize the cellular machinery to express viral genes and assemble progeny particles. In the same way, viral vectors represent the most effective means of gene transfer to modify specific cell type or tissue, and can be manipulated to express therapeutic genes.

Viral vectors are usually derived from parental wild type viruses whose viral genes (essential for replication and virulence) have been replaced with the heterologous genes intended for cell manipulation. They can be used as in vitro tools for biomolecular and gene functional studies, but also to accomplish more demanding tasks such as treat genetic disorders, fight cancer, drive tissue regeneration and monitor cell function.

In vitro and clinical use of viral vectors is based on RNA and DNA viruses that differ in their genomic structures and host range. Specific viruses have been picked as gene delivery vehicles according to their capacity to carry foreign genes, as well as their ability to conveniently deliver genes that are linked to efficient gene expression.

Key properties of viral vectors

Each viral vector system is characterized by an inherent set of properties that affect its suitability for gene therapy or other specific applications. To generate a vector, coding genes and so-called cis-acting regulatory sequences must be separated into distinct nucleic acid molecules in order to prevent their reconstitution and formation of productive viral particles.

Like all replication-incompetent vectors and viruses, viral particles can only be constructed if missing functions are superseded. This can be in a form of a helper virus, but a single helper plasmid encoding for a full-length defective helper virus genome can also be utilized.

Selection of the best-suited vector is pivotal and requires focused in-depth knowledge of the delivery systems and their performances. There is no one-fits-all multipurpose viral vector appropriate for all demands; rather, each of the vectors has its own advantages, limitations and range of applications.

Five classes of viral vector can be categorized in two principal groups, according to whether their genomes integrate into host cellular chromatin (lentiviruses and oncoretroviruses) or persist in the cell nucleus predominantly as extrachromosomal episomes (adenoviruses, adeno-associated viruses and herpes viruses).

Aforementioned distinction is an important determinant of the suitability of each vector for particular applications. In short, non-integrating vectors can facilitate persistent transgene expression in cells that do not proliferate, whereas integrating vectors represent a right choice if there is a need for stable genetic alteration in dividing cells.

Potential barriers

One of the first barriers that viral vectors have to bypass in the human organism is the immune response. Problems that may arise with gene transfer vectors include acute toxicity from the introduction of foreign materials, cellular and humoral immune responses directed against the transduced cells and products, as well as the potential for insertional mutagenesis by certain integrating vectors.

Furthermore, human trials have thus far used vectors that integrate into a relatively small percentage of cells within a target tissue. As more efficient vectors will target more cells, there is a possibility of inadvertent transmission into stem cells that capable of clonal growth and self-renewal, which subsequently raises important safety and ethical issues.

In conclusion, there is still a tremendous amount of work to be done in viral vector research. Continuous identification of potential hurdles and maintenance of a strong focus to improve vector systems will improve the promise gene therapy holds in treating a myriad of different diseases.


  6. Warnock JN, Daigre C, Al-Rubeai M. Introduction to Viral Vectors. In: Merten OW, Al-Rubeai M, editors. Viral Vectors for Gene Therapy: Methods and Protocols. Springer Science and Business Media, LLC, 2011; pp. 1-25.

Further Reading

  • All Viral Vector Content
  • Types of Viral Vectors
  • Viral Vector Applications
  • How is Adeno-Associated Virus Used as a Viral Vector?

Last Updated: Aug 23, 2018

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university – University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.

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