TOOLS OF THE TRADE

Genes are made of DNA. Successful gene delivery requires an efficient way to get the DNA into cells and to make it work. Scientists refer to these DNA delivery "vehicles" as vectors.

Choosing the best vector

There is no "perfect vector" that can treat every disorder. Like any type of medical treatment, a gene therapy vector must be customized to address the unique features of the disorder.

Part of the challenge in gene therapy is choosing the most suitable vector for treating the disorder.

Below, find out more about the most commonly used types of gene therapy vectors.

Viral vectors

Mother Nature is a brilliant scientist! Over the last three billion years or so, she's developed an incredibly efficient means of delivering foreign genes into cells: the virus.

Usually when we think of viruses, we think of them causing diseases such as the common cold, the flu, and HIV/AIDS. When faced with the problem of gene delivery, scientists looked to viruses. Why reinvent the wheel if there's a perfectly good one out there? If we can modify viruses to deliver genes without making people sick, we may have a good set of gene therapy tools.

General advantages of viral vectors:

• They're very good at targeting and entering cells.
• Some viral vectors might be engineered to target specific types of cells.
• They can be modified so that they can't replicate and destroy the cell.

General drawbacks of viral vectors:

• A virus can't "expand" to fit a piece of genetic material larger than it is naturally built to carry. Therefore, some genes may be too big to fit into a certain type of virus.
• Viruses can cause immune responses in patients, resulting in two potential outcomes:
  • Patients may get sick.
  • A patient's immunity to a virus may prevent him from responding to repeated treatments.

However, modern viral vectors have been engineered without most of the proteins that would cause an immune response.

Non-Viral Vectors

Although viruses can effectively deliver genetic material into a patient's cells, they do have some limitations. 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.

Scientists use bacteria and plasmids to easily and efficiently store and replicate genes of interest from any organism.

Ex vivo versus in vivo

Delivering genes to specific tissues within a patient's body can be very difficult. How can we do it?

Delivering genes into a group of cells in a patient's body can be done in one of two ways.

The first way is to inject the vector into the body and specifically target affected cells. This is called an in vivo (pronounced "in VEE-voh") approach.

The second way, called ex vivo (pronounced "ex VEE-voh"), is to deliver the gene to cells while they're outside the body by:

• Isolating the desired cells from the body.
• Culturing the cells in a Petri dish in the laboratory.
• Delivering the genes to the cells (using one of the vector options described on this page), activating them, and making sure that the cells integrate them properly.

Are there other tools?

The delivery methods described here are the most commonly used approaches to gene delivery, but they are not the only ones. For other delivery methods, see New Approaches to Gene Therapy.

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.