Discover the science of gene replacement therapy

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Gene replacement therapy is being studied as a treatment option for genetic diseases, and we want to help you understand the science behind it.

To begin, let’s talk about genes. Genes are small sections of DNA. DNA is inherited from your parents and carries instructions that tell the body how to function properly. Specific genes tell the body how to make specific proteins. Proteins play important roles in the body, like helping your cells to function properly or acting as the building blocks of your body. If a gene has an error, and the body can’t make a specific protein, it can be damaging to a person’s health.

A genetic disease or disorder is the result of an error in one or more of a person’s genes. The disease a person has depends on which gene in their DNA has the error. Depending on the disease or disorder, it can be inherited from one or both parents. Or, sometimes it’s a change that just happens randomly. A genetic disease caused by a single gene that is faulty or missing is called a monogenic disease.

We believe monogenic diseases are ideal targets for gene replacement therapy. Here’s why:

Gene replacement therapy is designed to target the root cause of a disease—the gene that doesn’t work properly—by delivering a new, working copy of the gene. The new gene carries the instructions for making the protein the body needs that it couldn’t make before. For example, the new gene may make a protein that is needed for cells to function properly. Once the protein is being made in those cells, there is the potential to stop disease progression. Time is critical because once cells lose their ability to function properly, they may not be able to be fixed, and any damage already done to the body may be irreversible.

So, how does gene replacement therapy work? In the lab, a new, working copy of a specific gene is made. Then, the new gene is put inside a delivery vehicle, called a vector. Vectors are chosen based on which type of cells in your body need the new gene. This is because vectors are very particular about the type of cell they choose to enter. For example, a certain vector may be used to deliver a gene to cells in the brain, while another vector may be used to deliver a gene to cells in the liver.

One type of vector is the adeno-associated virus, or AAV. AAVs are promising vectors because they are not known to make people sick. AAVs are able to travel through the body to target many different kinds of cells. When the AAV vector reaches the nucleus of the cell, it releases the working copy of the gene.

In this kind of gene replacement therapy, the new gene sits separate from your DNA, inside the nucleus, or control center, of the cell. The vector is then naturally broken down by the body, but the gene stays right where it was delivered. The gene starts working to make protein the body needs to work as it should.

Gene replacement therapy is a scientific advancement. For people who are living with monogenic diseases, it has the potential to create new treatment options and a new world of opportunities.

To learn more about gene replacement therapy, visit ExploreGeneTherapy.com.

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UNDERSTANDING GENE REPLACEMENT THERAPY

Gene therapy is a scientific technique that uses a working gene to treat or prevent diseases. Gene replacement therapy is a type of gene therapy that uses a “new gene” to replace a faulty or missing gene. Watch the video to learn how this approach attempts to address the root cause of genetic diseases.

What is a genetic disease?

Genes tell the body how to make important proteins that it needs to function. Genes come in pairs—one from each parent. A genetic disease is caused by a faulty or missing gene or genes. A genetic disease can be passed down from one or both parents or can be a result of random errors in the body’s genes.

What is a monogenic disease?

A monogenic disease is a disease caused by a single faulty or missing gene or gene pair. This can cause a problem in the body’s ability to make a needed protein. Nearly every function of the body is made possible by proteins. So, even if a single protein is missing, in short supply, or made wrong, the impact on the body can be very harmful.

We believe monogenic diseases could be ideal candidates for gene replacement therapy because they are caused by one gene.

Adult and child hands working together in a garden

What is the goal of gene replacement therapy?

Usually a person’s own genes each do their job to produce specific proteins.

In a person with a monogenic disease, there is one gene that is missing or does not work right. This results in either the protein being made incorrectly, made in short supply, or not made at all.

The goal of gene replacement therapy is to give the body a new working copy of the missing or faulty gene. This new gene may or may not become part of a person’s DNA and is able to give the body instructions for making a particular protein the body needs.

Usually a person’s own genes each do their job to produce specific proteins.

Person without a monogenic disease

A diagram of the genes of a person without a monogenic disease

In a person with a monogenic disease, there is one gene that is missing or does not work right. This results in either the protein being made incorrectly, made in short supply, or not made at all.

Person with a monogenic disease

A diagram of the genes of a person with a monogenic disease

The goal of gene replacement therapy is to give the body a new working copy of the missing or faulty gene. This new gene may or may not become part of a person’s DNA and is able to give the body instructions for making a particular protein the body needs.

Person treated with gene replacement therapy

A diagram of the genes of a person after being treated with gene replacement therapy

How does gene replacement therapy work?

A copy of a missing or faulty gene and a new working copy of the gene

1. Gene replacement therapy starts with scientists creating a new, working copy of a missing or faulty gene.

A gene within a vector (an envelope)

2. Then the new gene is placed inside a vector. A vector acts like an envelope. It carries the gene to the right places throughout the body.

Adeno-associated virus or AAV

3. A vector can be created by making changes to a naturally occurring virus. A virus is selected as a vector because of its ability to enter the body. One such virus, called an adeno-associated virus, or AAV, is used because it is not known to cause sickness in people.

A vector (an envelope) entering the body

4. Next, the vector enters the body and carries the new gene to the control center of the cells, also known as the nucleus.

A new gene

5. Once inside the nucleus, the new gene tells the body how to make the protein it needs. Finally, the rest of the vector is broken down by the body.

A historical look at gene therapy

Gene replacement therapy takes a different path to potential treatment because it addresses the root cause of the disease. Gene therapy, however, is not a new concept. Scientists have been exploring it as a way to treat genetic illness for decades.

A timeline of progress

  • Working with pea plants, a scientist named Gregor Mendel discovers the fundamentals of heredity and how genetic information is passed along.

  • The term “gene” is coined.

  • The adeno-associated virus (AAV) is discovered. It will eventually be modified by scientists and used as a vector to deliver a new gene to cells.

  • The concept of gene therapy is first considered as a treatment for genetic diseases.

  • Gene therapy is shown to be able to correct a genetic defect in human cells.

  • Gene therapy is used to treat a 4-year-old girl and a 9-year-old girl with a genetic disease.

    During this time, an 18-year-old boy undergoing gene therapy in a clinical trial passes away. This temporarily slows down gene therapy research so scientists can understand what happened. Scientists continue in their pursuit of a way to safely treat genetic diseases.

  • China approves the first gene therapy in the world for head and neck cancers.

  • Scientists show that an AAV vector has the potential to cross the blood-brain barrier in the body. This is a major advancement toward the treatment of genetic diseases with gene replacement therapy.

  • Over 1,800 gene therapy clinical trials have been completed, are ongoing, or have been approved worldwide at this point.

  • A gene therapy is approved for a genetic disease that causes blindness.

  • Many gene therapies for treating genetic diseases are being investigated in clinical studies.

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