In gene therapy, specific genes are targeted to address underlying genetic defects that cause diseases. The goal is to either repair, replace, or regulate the function of these genes in order to treat or prevent diseases. Let’s break down the types of genes that are typically targeted in gene therapy:
1. Defective or Mutated Genes
These are genes that have mutations causing them to malfunction. Mutations can lead to genetic disorders by producing faulty proteins or no protein at all. Gene therapy aims to correct or replace these defective genes.
Example:
CFTR Gene (Cystic Fibrosis): In cystic fibrosis, the CFTR gene is mutated. Gene therapy tries to introduce a normal copy of the CFTR gene into lung cells to restore its proper function.
2. Tumour Suppressor Genes
Tumour suppressor genes help regulate cell growth and prevent uncontrolled cell division, which can lead to cancer. When these genes are mutated, cells can grow out of control and form tumours. Gene therapy aims to restore or activate tumour suppressor genes to slow or stop cancer growth.
Example:
p53 Gene (Cancer): p53 is a well-known tumour suppressor gene. In some cancers, p53 is mutated, which leads to unchecked cell division. Gene therapy may introduce a functional version of p53 to promote normal cell death and reduce tumour growth.
3. Oncogenes
Oncogenes are genes that, when mutated or overactive, can cause cells to grow and divide uncontrollably, leading to cancer. The goal of gene therapy in this context is often to “turn off” or silence these overactive genes.
Example:
HER2 (Breast Cancer): HER2 is an oncogene that, when overexpressed, can drive the growth of breast cancer cells. Targeted gene therapies work to block or silence the action of HER2.
4. Genes Involved in Immune System Regulation
In diseases like cancer or autoimmune disorders, gene therapy can be used to modify genes that control immune responses. This can either boost the immune system to attack diseased cells (like in cancer) or suppress overactive immune responses (like in autoimmune diseases).
Example:
CAR-T Cell Therapy (Cancer): In CAR-T cell therapy, the patient’s T cells are genetically engineered to express a receptor that targets cancer cells. This enhances the immune system's ability to recognize and kill cancerous cells.
5. Genes Encoding Missing or Defective Enzymes
Some genetic disorders are caused by the absence or malfunctioning of enzymes necessary for vital chemical reactions in the body. Gene therapy introduces genes that code for these missing or defective enzymes to restore normal function.
Example:
ADA Gene (Severe Combined Immunodeficiency – SCID): Children with SCID (commonly known as “bubble boy” syndrome) lack the ADA enzyme. Gene therapy delivers a functional ADA gene to enable these patients to produce the enzyme and build a functioning immune system.
6. Genes that Promote Tissue Growth or Repair
In conditions where tissues are damaged (like heart disease or muscular dystrophy), gene therapy can target genes that stimulate tissue growth or repair.
Example:
VEGF (Vascular Endothelial Growth Factor – Heart Disease): VEGF is a gene that promotes blood vessel formation. Gene therapy targeting VEGF is used to stimulate new blood vessel growth in heart disease patients, improving blood flow to the heart.
7. Genes Related to Blood Disorders
Many blood disorders result from mutations in genes that affect the production of haemoglobin or other blood components. Gene therapy focuses on correcting these mutations to restore normal blood function.
Example:
HBB Gene (Sickle Cell Anaemia): The HBB gene, responsible for producing haemoglobin, is mutated in sickle cell anaemia. Gene therapy aims to replace the defective HBB gene with a healthy version, allowing patients to produce normal red blood cells.
8. Genes Controlling Apoptosis (Cell Death)
Apoptosis is the process of programmed cell death, which is crucial for removing damaged or unwanted cells. Some diseases, especially cancers, arise when apoptosis is impaired. Gene therapy can target genes to restore the normal cell death process.
Example:
BAX and BCL-2 Genes: These genes regulate apoptosis. BAX promotes apoptosis, while BCL-2 prevents it. In some cancers, BCL-2 is overexpressed, preventing cancer cells from dying. Gene therapy may target these genes to restore balance and induce the death of cancer cells.
Summary
In gene therapy, the choice of target genes depends on the disease being treated. These can include defective genes causing genetic disorders, tumour suppressor genes involved in cancer, oncogenes, genes regulating immune responses, and genes encoding enzymes or proteins critical to normal bodily function. By correcting or modifying these genes, gene therapy offers a promising approach to treating a wide range of genetic, infectious, and acquired diseases