The history and principles of retroviral vectors

Abstract

Retrovirus-derived gene transfer systems (retroviral vectors) are the most commonly used gene transfer tools in modern biology. They have been used to study various aspects of retroviral replication, the organization and function of oncogenes and other eucaryotic genes, and, recently, to transduce therapeutic genes to cure inborn errors of metabolism, cancer, AIDS, and many other diseases in man. Highly oncogenic retroviruses served as a model for the construction of artificial retroviral gene transfer systems. These viruses carry a non-viral gene in their genome in addition or substituting for viral protein coding sequences. The replication of such defective retroviruses depends on the presence of a wild-type-virus, which supplies all proteins in trans for particle assembly and infection of a new target cell. Thus, highly oncogenic retroviruses can be considered as naturally occurring gene transfer vectors. Following this principle, cell lines have been constructed which express retroviral protein coding sequences from plasmid DNAs and which contain a viral genome in which the protein coding sequences have been replaced with a gene of interest. This article describes the history, principles, and basic building blocks of first and modern retrovirus-derived gene transfer systems.

N-Terminally Myristoylated Feline Foamy Virus Gag Allows Env-Independent Budding of Sub-Viral Particles

“…In this context, requirements important for virus transmission and survival in the host must not automatically fit those relevant for gene transfer or vaccine antigen expression. Thus, molecular dissection of these processes is not only aimed at increasing our overall understanding of the molecular biology of the corresponding viruses, but may also help to exploit or even optimize the mechanisms identified [3]. …”

Inhibition of histone deacetylation in 293GPG packaging cell line improves the production of self-inactivating MLV-derived retroviral vectors

“…For this reason, they have been a favored method of gene transfer into dividing cells in approaches where stable and sustained gene expression is desired or necessary. Conventional retroviral vectors resemble in their architecture their wild-type counterparts in that they retain cis -acting promoter sequences located in the 5' and the 3' long terminal repeats (LTRs) and the Ψ signal that allows the packaging of recombinant RNA into viral particles [ 1 , 2 ].…”

Gene therapy in cartilage damage

“…È stato il primo vettore utilizzato in terapia genica. Il lentivirus ha un'alta efficienza di trasduzione con una persistente espressione del transgene; infetta sia "dividing cell" sia "non-dividing cell"; l'uso dei lentivirus nella traduzione nelle cellule umane è complicato dalla loro sensibilità all'inibizione da parte del complemento [67][68][69][70][71][72][73]. I vettori non virali, anche se meno efficienti rispetto ai vettori virali, sono meno costosi e non danno reazioni immunologiche e infettive, e dunque sono ancora tenuti in considerazione.…”