Building a Gene Replacement Therapy

What are the key components of gene replacement therapy?

There are 2 main parts to gene replacement therapy: genes and vectors.

A gene


A new, working human gene is designed to give the cell the instructions it needs to make the protein that is missing or in short supply.

This new gene is created in a laboratory and is specific to the disease being treated. That is, scientists work to discover which gene needs to be replaced and figure out how to create the new, working gene. This is one reason why a single gene replacement therapy can take many years—even decades—to research and produce.

A gene inside a vector


Vectors are the delivery vehicles used to carry a new, working copy of the missing or nonworking gene into the right cells inside the body. These delivery vehicles are typically made from naturally occurring viruses. Viruses are used because they are very good at getting inside of cells. However, scientists remove DNA from the virus so that it won’t make people sick when used as a vector.

Virus DNA removed/Working gene added

A commonly used virus is the adeno-associated virus, or AAV. It was first discovered in 1965. It is used because it can get inside many different types of cells, such as those in the liver, kidney, eyes, and the central nervous system (see diagram below). There are several different types of AAVs, and each has a specific affinity for certain types of cells in people, allowing them to target different cells and tissues. AAV is also not known to cause illness in people. This makes the AAV a potentially promising vehicle for use in the treatment of a wide range of genetic diseases.

AAVs targeting many different cell types

Other viruses are also being researched as possible vectors for use in gene replacement therapy. Because each of these viruses have unique sets of characteristics, their use as a vector may be better suited for one genetic disease over another. For example, some viruses are naturally able to put genetic information into your DNA (integrating), while others leave it separate (nonintegrating).

  • Integrating viral vectors could be important for genetic diseases that occur in cells that frequently copy themselves. This would enable the new cells to keep producing the genetic information with the intended effect
  • Nonintegrating viral vectors could be better suited for use in cells that didn't copy themselves often, such as brain or liver cells, because the new cells would not carry the genetic information

Current gene replacement therapy advancements are the result of nearly a century of research.

Explore the many major milestones that have made gene-based therapies a possibility today.

Check your understanding of gene replacement therapy


What does the new gene do?

Once the vector delivers the new gene to the cells, it then provides the instructions needed to make the protein that is missing or in short supply.

Can the viral vector make you sick?

While the vehicles used to carry the new gene into the nucleus of the cells are typically made from naturally occurring viruses, scientists have made changes to them so that they don’t make you sick. AAV, one type of virus used as a vector, is not known to cause sickness in humans.

Learn more about how gene replacement therapy is different than other gene-based therapies.