Gene therapy is a category of treatment that alters a person’s genes to treat or cure a disease. This is accomplished by delivering genetic material to cells in the body to replace or repair damaged genes. There are two broad approaches to gene therapy treatment, in vivo and ex vivo, and each relies on a different gene vector to get the job done. Let’s take a closer look.

Viva In Vivo

In vivo gene therapy involves delivering genetic material directly to cells within the body, typically using vectors. Common vectors include viral vectors, genetically modified harmless viruses designed to bind to cells and transport the genetic material, and non-viral vectors like lipid nanoparticles (LNPs), which effectively package the genetic material for delivery to target cells.

The Ex Factor

Ex vivo gene therapy involves delivering genetic material to cells extracted from the body. Once removed, these cells are genetically corrected in a laboratory setting before being reintroduced into the patient. Standard methods for fixing genetic defects in these extracted cells are CAR-T and CRISPR technology.

Viral Vectors Explained

Adeno-associated viruses (AAVs) and lentiviruses are commonly used viral vectors in gene therapy, but they are suited for different applications. AAVs are favored for targeted delivery to non-dividing cells, while lentiviruses target dividing cells. AAVs are primarily used for in vivo gene therapy applications. Lentiviruses integrate into the genome and provide long-term expression for ex vivo gene therapies.

AAV Focus

AAVs are used for a variety of genetic disorders and form the basis of several approved products:

• Spinal Muscular Atrophy (SMA): AAVs, such as in Zolgensma (onasemnogene abeparvovec-xioi), deliver a functional copy of the SMN1 gene.
• Leber Congenital Amaurosis: Luxturna (voretigene neparvovec-rzyl), an AAV, treats inherited blindness by delivering the RPE65 gene.
• Hemophilia B: AAVs like Hemgenix (etranacogene dezaparvovec), deliver clotting factor genes.

Lentivirus Focus

Lentiviruses are typically used when stable, long-term expression of the therapeutic gene is required. They are particularly suited for conditions such as cancer and blood disorders.

• Beta-thalassemia: Lentiviral vectors such as Zynteglo (betibeglogene autotemcel) deliver a modified beta-globin gene to a patient’s hematopoietic stem cells.
• B-cell lymphoma: Yescarta (axicabtagene ciloleucel) is a CAR-T therapy that modifies a patient’s T-cells to target and attack cancer cells. Specifically, it delivers a synthetic gene that encodes a chimeric antigen receptor (CAR) targeting the CD19 protein. By expressing this CAR, the modified T-cells can recognize and eliminate cancerous B-cells expressing CD19.

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Cocktail Fodder

A new in vivo gene therapy treatment recently restored partial hearing in five of six congenitally deaf children. The viral vector used in this clinical trial introduces a working copy of the OTOF gene to cells in the cochlea located in the inner ear.