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Production of Lentiviral Vectors for Transducing Cells from the Central Nervous System
Published on: May 24, 2012
The retroviral life cycle and the molecular construction of retrovirus vectors
1Chester Beatty Laboratories, Institute of Cancer Research, London, UK.
Abstract:
The discovery of a filterable agent that allowed the transmission of cancers in chickens (1) was the first identification of the viruses now known as retroviruses. Subsequently, genes transmitted by some retroviruses were identified as transforming oncogenes. These findings suggested that retroviruses may be used as genetic vectors, since retroviral oncogenes (v-onc) are altered forms of "highjacked" normal cellular genes (2), and the retroviruses that transform cells in culture are often defective for replication because the v-onc genes have been substituted in place of one or more of the essential replicative genes (3). Such defective oncogenic retroviruses can be propagated only in the presence of a wild-type "helper" virus, which supplies the functional gene products of the virus. Retroviruses can now be modified to become vehicles for the delivery and expression of cloned genes into a wide variety of cells, for both experimental and therapeutic purposes.
Insights
Retroviruses, initially identified as cancer-causing agents in chickens, can be engineered as genetic vectors. These modified retroviruses deliver and express cloned genes for research and therapeutic applications.
Area of Science:
- Virology
- Molecular Biology
- Cancer Research
Background:
- The discovery of filterable cancer-transmitting agents in chickens led to the identification of retroviruses.
- Retroviruses were found to carry transforming oncogenes, which are altered forms of normal cellular genes.
- Some oncogenic retroviruses are replication-defective due to oncogene substitution for essential viral genes.
Purpose of the Study:
- To explore the potential of retroviruses as genetic vectors.
- To understand the mechanism of retroviral oncogene transfer and replication.
- To highlight the utility of modified retroviruses for gene delivery.
Main Methods:
- Identification of filterable cancer-transmitting agents in chickens.
- Analysis of genes transmitted by retroviruses, identifying transforming oncogenes (v-onc).
- Characterization of replication-defective oncogenic retroviruses and their dependence on helper viruses.
Main Results:
- Retroviruses were identified as agents capable of transmitting cancer.
- Retroviral oncogenes (v-onc) were recognized as critical for cellular transformation.
- Defective oncogenic retroviruses require helper viruses for propagation.
Conclusions:
- Retroviruses can be modified into effective genetic vectors.
- These vectors facilitate the delivery and expression of cloned genes.
- Applications span both experimental research and therapeutic interventions.
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