Viral Vectors Overview

Summary

Gene therapy aims to treat specific diseases by introducing, removing, or modifying genetic material in cells. This is often achieved using viral vectors, which deliver therapeutic genes to target cells. Adeno-associated viruses (AAVs), adenoviral vectors, and lentiviral or retroviral vectors each have unique properties and applications in gene therapy. AAVs are safe for non-dividing cells but have limitations due to pre-existing immunity. Adenoviral vectors can deliver larger genetic packages but may cause immune responses. Lentiviral and retroviral vectors integrate into the target cell's genome, making them ideal for ex vivo treatments. Gene therapy is already being used for rare hereditary diseases and cancers, with ongoing research into its potential.

Takeaways

• 😀 Gene therapy aims to treat specific diseases by modifying genetic material (DNA or RNA) in a person's cells.
• 😀 Vectors, often derived from viruses, are used to deliver therapeutic genetic material directly into cells.
• 😀 Viral vectors are modified to remove viral genes and only carry therapeutic genes, ensuring safety in humans.
• 😀 The virus shell (capsid) of viral vectors acts as a delivery mechanism for the therapeutic genes, like an envelope carrying a message.
• 😀 Researchers use only viral vectors that have been extensively studied and proven safe for human use.
• 😀 Adeno-associated viruses (AAV) are commonly used to deliver small DNA packages and are ideal for non-dividing cells like those in the liver, nervous system, eyes, and skeletal muscles.
• 😀 AAV vectors do not integrate into the host cell's genome, meaning the therapeutic gene may not persist long-term in dividing cells.
• 😀 A major challenge is that many people have prior exposure to AAVs, resulting in immune responses that could destroy the vector before it delivers its therapeutic genes.
• 😀 Adenoviral vectors can deliver larger genetic packages but previously caused strong immune responses that led to inflammation and reduced therapy effectiveness.
• 😀 Lentiviral and retroviral vectors are used for ex vivo therapies, delivering larger genetic packages to dividing cells, and integrate into the target cell's genome for long-term effects.
• 😀 Ex vivo therapy involves removing cells from the body, modifying them with gene therapy, and returning them to the body, where they divide and replicate the therapeutic genes.
• 😀 Gene therapy with viral vectors is already being used to treat rare inherited diseases and certain forms of cancer, with ongoing research exploring additional applications.

Q & A

What is the main objective of gene therapy?

The main objective of gene therapy is to treat a specific disease by introducing, removing, or modifying genetic material (DNA or RNA) in a person's cells.

How do viral vectors work in gene therapy?

Viral vectors deliver therapeutic genetic material, such as a functional gene, directly into a cell. These vectors are derived from viruses, but the viral genes are removed and modified for safety, only carrying therapeutic genes.

Why are viral vectors commonly used in gene therapy?

Viral vectors are commonly used because viruses are very efficient at penetrating cells. By removing the viral genes and modifying the vector, they can safely deliver therapeutic genes without causing disease.

What are the four main types of viral vectors in gene therapy?

The four main types of viral vectors in gene therapy are adeno-associated vectors (AAV), adenoviral vectors, lentiviral vectors, and retroviral vectors.

What is the characteristic of adeno-associated vectors (AAV) in gene therapy?

AAVs are used to deliver smaller packages of DNA or genes. They are safe and efficient for in vivo gene therapy but do not integrate into the cell's genome, which may limit long-term effectiveness.

Why are AAVs commonly used for liver, nervous system, eye, and skeletal muscle treatments?

AAVs are ideal for treating cells that do not divide, like those in the liver, nervous system, eyes, and skeletal muscles, as they do not integrate into the genome, which prevents the loss of the therapeutic gene over time.

What challenge is associated with the use of AAV vectors in gene therapy?

A major challenge with AAV vectors is that many people may have pre-existing immunity due to previous exposure to AAVs, which can cause the immune system to attack the vector before it delivers the therapeutic gene.

How have researchers addressed immune responses to AAV vectors?

Researchers are working on various strategies to reduce immune responses to AAV vectors, allowing them to effectively deliver genetic material without triggering harmful immune reactions.

What is the key difference between adenoviral vectors and AAV vectors?

Adenoviral vectors can carry much larger genetic packages (almost eight times the size of AAVs). However, early versions of adenoviral vectors caused severe immune responses, prompting the development of newer, safer versions.

What is the purpose of lentiviral and retroviral vectors in gene therapy?

Lentiviral and retroviral vectors are used for ex vivo gene therapy, where cells are modified outside the body and then reintroduced. These vectors can integrate into the cell's genome, making them suitable for treating dividing cells, such as T-cells and stem cells.

What is the process of ex vivo gene therapy?

Ex vivo gene therapy involves removing cells from a patient's body, modifying them with therapeutic genetic material, and then returning them to the body. The treated cells divide, and the new genetic material is copied into all the resulting cells.

What are the potential uses of gene therapy beyond hereditary diseases and cancer?

Gene therapy has many potential uses under investigation, including treatments for various genetic disorders, autoimmune diseases, and other conditions where altering genetic material could provide therapeutic benefits.