Gene Delivery: The Key to Gene Therapy

In Choosing Targets for Gene Therapy, we saw that cystic fibrosis is a good candidate for gene therapy. This is because:

• We know which gene is mutated in the disorder.
• We have a normal copy of that gene available.
• We understand the biology of the disease, including which tissue types are affected and how they are affected.
• We can predict that adding the normal gene back to the cells that make up the affected tissues will restore a needed function.

Now all we have to do is deliver the gene into the proper cells and put it to work. This is not an easy job. Gene delivery is one of the biggest challenges in the field of gene therapy.

What are some of the hallmarks of successful gene delivery?

1. TARGETING the right cells. If you want to deliver a gene into cells of the liver, it shouldn't wind up in the big toe. How can you ensure that the gene gets into the correct cells?

2. ACTIVATING the gene. A gene's journey is not over when it enters the cell. It must go to the cell's nucleus and be "turned on," meaning that its transcription and translation are activated to produce the protein product encoded by the gene. For gene delivery to be successful, the protein that is produced must function properly.

3. INTEGRATING the gene in the cells. You might want the gene to stay put and continue working in the target cells. If so, you need to ensure that the gene integrates into, or becomes part of the host cell's genetic material, or that the gene finds another way to survive in the nucleus without being trashed.

4. AVOIDING harmful side effects. Anytime you introduce an unfamiliar biological substance into the body, there is a risk that it will be toxic or that the body will mount an immune response against it. If the body develops immunity against a specific gene delivery vehicle, future rounds of the therapy will be ineffective.

Explore some of the gene delivery methods that researchers have developed in Tools of the Trade.

Supported by a Science Education Partnership Award (SEPA) [No. 1 R25 RR16291-01] from the National Center for Research Resources, a component of the National Institutes of Health, Department of Health and Human Services. The contents provided here are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH.