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14 Jun 2012

Vectors and meganucleases: explanations

Illustration for article: Vectors and meganucleases: explanations
Vectors are gene-drug "shuttles" whereas meganucleases are "DNA scissors". They are tools which are essential for gene therapy and gene surgery. This is why the French Muscular Dystrophy Associationg (AFM-Téléthon) supports their production.

What is a vector?

A vector is used to transport the gene-drug inside the cell. There are physical vectors such as electroporation and biolistics, and synthetic vectors (chemical compounds which bind to the gene-drug), but the most frequent vectors are biological: modified viruses or plasmids.

Indeed, viruses have a tremendous ability to penetrate cell membranes and insert their DNA into the nucleus in order to modify our cell machinery to their benefit, by having their own proteins produced by our cells. By modifying them so that they lose their pathogenic character, these properties can be used for inserting the gene-drug into the viral DNA, then letting nature take action.

Types of viral vectors

Several types of viral vectors have been developed. The first, retroviruses, are gradually being abandoned because they are judged to be too risky because of the random integration of their DNA with cell DNA, leading to a risk of cancer. The use of adeno-associated or adenoviruses and lentiviruses is expanding.

As for plasmids, these are small strands of naked circular DNA which can multiply autonomously.  They are essential for producing viral vectors but can also be used directly as gene-drug vectors. With plasmids there is less risk of inducing an immune reaction than with AAV vectors, but gene transfer via a plasmid has been less successful.

Meganucleases

Meganucleases are DNA scissors used to cut out an anomaly in a gene. They are used in gene surgery.

AFM-Téléthon has signed a research contract and license with the French leader in meganuclease production, Cellectis, which plans to produce batches of meganucleases for seven types of genetic mutations. The first two genes concerned are those of beta globin, the deficiency of which causes blood and dystrophin-linked diseases leading to Duchenne and Becker muscular dystrophy.