There are several types of viral vectors that can be used to deliver nucleic acids into the genetic makeup of cells, including retrovirus, lentivirus, adenovirus, adeno-associated virus and herpes simplex virus. Each of these has unique advantages and disadvantages for specific applications, as outlined below.
Retroviral Vectors
Retroviral vectors are commonly used and known to integrate into the genome of the infected cell in a stable and permanent fashion. Reverse transcriptase in the virus allows integration into the host genome.
There are two types of retroviral vectors: replication-competent and replication defective. Usually replication-defective vectors are preferred in practice as they allow for several rounds of replication due to their coding regions.
However, for transduction to occur retrovirus cells require mitotic cell division to be in process, which puts a significant limit on their utility. Because of this, some cells such as neurons are resistant to the effect of retroviral vectors.
Lentiviral Vectors
Lentiviruses are a type of retrovirus that are able to integrate into non-dividing cells and do not require mitotic cell division in order to function. Instead, the genome enters the cell DNA via reverse transcription and is incorporated in a random position of the cell genome.
The unpredictability of the integration site is a significant inhibitory factor of this type of vector. It may lead to a disturbance in cellular function and has the potential to lead to cancer development. Despite this, research is supportive of the use of lentivirus as a vector and has demonstrated that the risk of negative consequences is low.
Adenoviral Vectors
Adenoviral vectors have a wide range of action and are able to deliver nucleic acids to both dividing and non-dividing cells. This can make their use in basic research difficult, but they are sometimes used in vitro. When utilized in vivo, adenoviral vectors often precipitate immune elimination of the cells, which also limits their functionality.
Adenoviruses are often responsible for respiratory, gastrointestinal and eye infection that affect humans. As a result, research is currently being conducted to investigate the use of adenoviral vectors in applications of gene therapy and vaccination.
Adeno-associated viral vectors
Similarly to adenoviral vectors, adeno-associated viral (AAV) vectors can deliver genetic material to dividing and non-dividing cells. It is a small virus that is known to affect humans with a very mild immune response. As a result AAV vectors have beneficial properties for gene therapy that are effective with limited negative effects. However, the utility of this type of vector is significantly limited by its restricted capacity of DNA.
Herpes Simplex Virus Vectors
This type of viral vector has the ability to deliver large-scale quantities of exogenous DNA. The primary concerns with the use of herpes simplex virus to deliver genetic material are cytotoxicity and the maintenance of transgene expression.
Chimeric Viral Vectors
Chimeric viral vectors may be constructed to combine the properties of several types to manipulate the advantages and disadvantages of the vectors. These are not widely used at present, but are a promising solution for the future when their properties have been established further.
References
Gene Therapy Contract Development and Manufacturing: Challenges and Future Perspectives