Passage #006

      Successful gene delivery requires efficient vehicles to deliver the therapeutic genes to the appropriate host cells. In addition, these vectors must allow for highly specific insertion of the gene into host DNA. As each hereditary disorder is genetically unique, gene therapy vectors must be customized to address the unique features of each. One of the greatest challenges in gene therapy is choosing the most suitable vector for treating the disorder.

       In general, gene therapy vectors are classified as viral, or non-viral. Viruses ‘infect’ by injecting their genes into host cells and employing host cellular machinery to express their genes. Thus, viruses are an instinctive choice for injecting therapeutic DNA into genetically vulnerable cells. By modifying viruses, scientists may target the vectors to specific cell types, and avoid host immune responses.

       Although the vectors may be modified to suppress viral gene expression, they have a limited carrying capacity. Viruses are each unique in the size of gene they may transport.

       It is sometimes more efficient to deliver a gene using a non-viral vector, which has fewer size constraints and which won't generate an immune response. Non-viral vectors are typically circular DNA molecules, also known as plasmids. In nature, bacteria use plasmids to transfer genes from cell to cell. 

 

Figure 1. Carrying capacity and genetic makeup of common viral vectors

Vector	Genome Type	Genome Size
Adenovirus	dsDNA	7500 bp
Retrovirus	+RNA	8000 bp
Adeno-associated virus	ssDNA	5000 bp
Herpes simplex virus	ssDNA	20000 bp