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Gene Therapy

2. Mode of action

There are three main gene therapy strategies:
  1. Adding a ‘corrected’ copy of the gene.
  2. Knocking down or inactivating a mutated gene that is not functioning normally.
  3. Repairing a faulty gene.

In the first strategy of introducing a corrected copy of the gene into the body, the DNA has to be inserted in suitable packaging, called a vector. The vector protects the DNA from degradation and ensures that the gene is delivered efficiently to the target cells. Viral vectors are commonly used for gene therapy because viruses are highly effective in delivering genetic material into human cells. While the diseased cells will still produce the faulty protein, the presence of the new gene will mean that the cell will start to produce normal proteins as well. Some functionality will be restored, which should have a therapeutic benefit.

Knocking out a gene refers to the prevention of damaged proteins being made. When a protein is made, a ribonucleic acid (RNA) copy of the gene is made and transported out of the nucleus into the part of the cell where the protein synthesis machinery is located. Protein-coding RNA can be inhibited and targeted for destruction by small RNA molecules with a complementary sequence, thus preventing the faulty proteins from being synthesised by the cell.

The final gene therapy strategy is to repair the mutation in the DNA. This approach is high-risk as it involves altering the original DNA blueprint of the cell. As of 2014, this type of genetic engineering has not yet been tested in humans but has been used in human cell lines in the laboratory. This technique involves cutting out damaged sections of DNA and replacing them with the correct sequence.

The gene therapy vector can be introduced directly into the body via injection or inhalation, or cells can be modified in the laboratory before insertion into the body. Once the gene therapy vector is inside the body it will deliver its cargo to cells and the DNA will become integrated into DNA in the nucleus in some cases. The cell will use this new DNA to start making corrected copies of the protein.