8 Biotechnology- Biology for Human Welfare
8.4 Gene therapy
Gene Therapy
Dr V Malathi
Gene therapy is a cutting-edge biomedical procedure that includes changing or modifying genes. Gene therapy is used to restore normal function in cells, it is used to repress malfunctioning genes,it introduce therapeutic genes, or fix damaged genes. Gene therapy has enormous promise for treating cancer, genetic abnormalities, and other illnesses brought on by defective or missing genes.Both inherited genetic diseases (e.g., hemophilia and sickle cell disease) and acquired disorders (e.g., leukemia) have been treated with gene therapy.
How Does Gene Therapy Work?
The process of gene therapy involves adding, deleting, or changing genetic material in a patient’s cells.
The three main strategies of gene therapy include:
- Replacing a Mutated Gene : A functional copy of a gene is substituted for a defective or absent one.
Example: Replacing the faulty ADA gene to treat severe combined immunodeficiency (SCID). - Inactivating a Faulty Gene : A disease-causing gene that isn’t working properly is switched off.
For instance, turning off genes that encourage the growth of cancer. - Introducing a New Gene : To aid the body in fighting sickness, a whole new gene is added.
For instance, introducing genes to create therapeutic proteins to treat conditions like hemophilia.
Types of Gene Therapy
a. Germline Gene Therapy : Involves altering the DNA of germ cells, such as sperm, eggs, or embryos. Future generations will be affected by these inherited alterations.
Applications include the potential to treat hereditary illnesses like Huntington’s disease and cystic fibrosis while they are still in the embryonic stage. This type of gene therapy is not approved for use in humans in the majority of nations due to ethical considerations.
frequently used to treat genetic problems in diseases like cancer, and hemophilia.
a.In Vivo Gene Therapy: In this method the therapeutic gene is introduced into the patient’s body directly in to the target organs or tissues. It makes use of either non-viral or viral vectors. Example :Direct gene injection into muscle tissue to treat genetic diseases like muscular dystrophy. Challenges include accuracy in targeting, avoiding off -targets.
b. Ex Vivo Gene Therapy: Here cells from the patient are taken out, genetically altered in a lab, and then reintroduced into the body. This type of therapy is used in CAR-T Cell Treatment which involves altering immune cells to specifically target cancer. This type of therapy is advantageous as the controlled environment reduces risks of unintended effects.
Based on Therapeutic Approach
a. Gene Augmentation Therapy : This is the addition of a functional gene to replace a missing or damaged gene.
This is used for treating illnesses like muscular dystrophy and cystic fibrosis brought on by mutations that induce loss of function.
b. Gene silencing therapy : is defined as suppressing the expression of genes that are dangerous or dysfunctional.
Applications include silencing genes that support viral replication or malignancy by using RNA interference (RNAi) or antisense oligonucleotides.
c.Gene Editing Therapy : Directly alters the DNA using genome editors like CRISPR-Cas9.Applications include introducing therapeutic sequences for targeted therapies or fixing point mutations.
d. Suicide Gene Therapy: Introduces a gene that generates toxic compounds to destroy particular cells, like cancer cells.Applications include cancer therapies that only target tumor cells.
e. Immune-Modulatory Gene Therapy: Boosts or alters the immune system to combat illnesses, especially infections and malignancies. Applications include modifying T cells to target malignancies in CAR-T treatment.
Based on Vectors Used
1. Viral Gene Therapy : Delivers therapeutic genes by means of genetically modified viruses, such as lentivirus and adenovirus. It is highly effectiveness but could elicit immunological reactions.
The use of an adenovirus vector may cause an unexpected inflammatory immunological response in certain patients, which could result in organ failure. Furthermore, as viruses frequently target more than one type of cell, the virus vector may infect cells that are not the target of the therapy, harming those cells and potentially causing diseases like cancer. Another possible danger is that the altered virus can become contagious again and infect the patient. Last but not least, the inserted gene may inadvertently deactivate another crucial gene in the patient’s genome, interfering with regular cell cycle and perhaps resulting in the development of tumors and cancer.
” Gene therapy using an adenovirus vector can be used to treat or cure certain genetic diseases in which a patient has a defective gene” by modification of work by National Institutes of Health via Lumen learning is licensed under CC BY 4.0
2. Non-viral gene therapy makes use of physical techniques (such as electroporation) or synthetic vectors like liposomes or nanoparticles. It is less effective than viral techniques, but safer.
Some of the types of Non-Viral Gene Delivery Systems include :
a. Electroporation : Uses electrical pulses to create temporary pores in the cell membrane, allowing DNA or RNA to enter.
b. Gene Gun (Biolistics) :DNA is coated onto microscopic particles (often gold or tungsten) and “shot” into cells using high velocity.
c. Ultrasound (Sonoporation) : High-frequency sound waves generate microbubbles that temporarily disrupt cell membranes, facilitating DNA/RNA entry.
d.Liposomes (Lipid-Based Nanoparticles) : Lipid molecules encapsulate DNA or RNA in vesicles, which merge with the cell membrane to deliver their cargo.
Gene Therapy for Cystic Fibrosis
A promising treatment option for cystic fibrosis (CF), a hereditary condition brought on by mutations in the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene, is gene therapy. A protein that controls the flow of water and salt into and out of cells is encoded by this gene. Severe respiratory and gastrointestinal problems are caused by mutations in the CFTR gene, which cause thick, sticky mucus to accumulate in the lungs, digestive tract, and other organs.
Cystic Fibrosis Gene Therapy aims to replace or repair the faulty CFTR gene to restore normal protein function.
Gene therapy for Severe Combined Immunodeficiency (SCID)
A collection of uncommon illnesses known as severe combined immunodeficiency (SCID) are brought on by abnormalities in many genes essential to the growth and operation of immune cells that fight infection. Although they seem healthy at birth, infants with SCID are more vulnerable to serious illnesses. Unless babies get immune-restoring therapies such gene therapy, enzyme therapy, or blood-forming stem cell transplants, the illness is deadly, usually within the first year or two of life.
The most common inheritance pattern for SCID is autosomal recessive, meaning that both copies of a given gene—one from the father and one from the mother—have flaws. Adenosine deaminase (ADA) deficiency, in which babies lack the ADA enzyme required for T-cell survival, is the most well-known type of autosomal recessive SCID. Male newborns are the main victims of X-linked SCID, which is brought on by mutations in a gene on the X chromosome. White blood cells in boys with this kind of SCID proliferate and develop abnormally. They consequently have low levels of natural killer cells and T cells, and their B cells are dysfunctional.
Watch the video from National Institute of Health on Gene Therapy for X-Linked SCID