In the most straightforward cases, gene therapy adds a functional copy of a gene to cells that have only non-functional copies.Gene Delivery: Tools of the Trade summarizes the viral and non-viral vectors most commonly used for this type of gene delivery.
But there are times when simply adding a working copy of the gene won't solve the problem. In these cases, scientists have had to think outside the box to come up other approaches.
To address the below situations, you could prevent the cell from making the protein the gene encodes, repair the gene, or find a work-around aimed at blocking or eliminating the protein.
Some mutations in genes lead to the production of a dominant-negative protein. A dominant-negative protein may block a normal protein from doing its job (for an example, see Pachyonychia congenita). In this case, adding a functional copy of the gene won't help, because the dominant-negative protein will still be there causing problems.
A gain-of-function mutation makes a protein that acts abnormally, causing problems all on its own. For example, let's say a signal activates protein X, which then tells the cell to start growing and dividing. A gain-of-function mutation may make protein X activate cell growth even when there's no signal, leading to cancer.
Sometimes a disorder can involve a protein that is functioning as it should—but there's a problem with where, when, or how much protein is being made. These are problems of gene regulation: genes need to be turned "on" in the right place, at the right time, and to the right level.