12.4 Gene Therapy
3 min read•june 18, 2024
is a groundbreaking approach to treating genetic disorders. It works by introducing functional genes into cells to replace or correct faulty ones. This revolutionary technique offers hope for curing diseases like and certain cancers.
There are different methods for delivering genes, including and non-viral approaches. While shows immense promise, it also comes with and ethical concerns. These include potential immune responses, unintended genetic changes, and debates about modifying human traits.
Gene Therapy: Mechanisms, Applications, and Ethical Considerations
Mechanisms of gene therapy
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- Gene therapy introduces functional genes into cells to replace or correct defective genes
- Viral vectors commonly deliver therapeutic genes into target cells
- , , and (AAVs) are popular choices due to their ability to efficiently infect cells and integrate the therapeutic gene () into the host genome
- Non-viral methods, such as or naked DNA injection, offer an alternative gene delivery approach that avoids the use of viral vectors and their associated risks
- Viral vectors commonly deliver therapeutic genes into target cells
- Potential applications include treating genetic disorders caused by single-gene defects
- , , , and certain types of cancer (, ) are examples of diseases that could benefit from gene therapy
- Introduces genes that enhance the immune system's ability to fight cancer () or infectious diseases (HIV, hepatitis)
- Future applications may extend to treating complex genetic disorders (, ) and acquired diseases (cardiovascular disease, diabetes)
Gene therapy approaches
- : Cells are modified outside the body and then reintroduced
- : Genetic material is delivered directly into the patient's body
- : Precise modification of DNA sequences using tools like
Risks vs benefits of gene therapy
- Benefits:
- Potential to cure or significantly improve symptoms of genetic disorders, providing long-term or permanent treatment and reducing the need for ongoing medical interventions
- Could be more cost-effective than traditional treatments in the long run by addressing the underlying genetic cause rather than managing symptoms
- Risks and challenges:
- Immune responses to viral vectors or the introduced gene product can limit the effectiveness of the therapy and cause adverse reactions
- : unintended insertion of the therapeutic gene into the host genome, potentially causing cancer (leukemia) or other adverse effects
- : the introduced gene may affect unintended tissues or cells, leading to undesirable side effects
- Limited duration of gene expression may require repeated treatments to maintain therapeutic benefits
- Ethical concerns regarding the potential misuse of gene therapy technologies, such as enhancing human traits for non-medical purposes
Somatic vs germ-line gene therapy
- :
- Modifies non-reproductive cells (somatic cells) in the patient's body
- Effects are limited to the treated individual and not passed on to future generations
- Generally considered less ethically controversial than
- Regulatory oversight focuses on ensuring safety and efficacy for the treated individual
- :
- Modifies reproductive cells (germ cells) or early embryos
- Genetic modifications are passed on to future generations, raising concerns about the long-term consequences and the idea of "designer babies"
- Currently prohibited in many countries due to ethical and safety concerns
- Regulatory oversight is more stringent and focuses on long-term effects and societal implications
- Ethical implications and considerations:
- Balancing the potential benefits of treating genetic disorders with the risks and uncertainties associated with gene therapy
- Ensuring equal access to gene therapy treatments and preventing genetic discrimination based on an individual's genetic profile
- Addressing the potential for misuse, such as using gene therapy for non-medical purposes (athletic enhancement) or enhancing human traits (intelligence, appearance)
- Engaging in public discourse and education to foster informed decision-making and policy development around the use of gene therapy technologies
Key Terms to Review (43)
Adeno-Associated Viruses: Adeno-associated viruses (AAVs) are small, non-enveloped, single-stranded DNA viruses that belong to the Dependovirus genus. They are considered helper-dependent, as they require the presence of a helper virus, such as an adenovirus or herpes virus, to complete their replication cycle.
Adenosine deaminase deficiency: Adenosine deaminase deficiency (ADA deficiency) is a genetic disorder that affects the immune system by impairing the breakdown of adenosine and deoxyadenosine. This leads to severe combined immunodeficiency (SCID), making individuals highly susceptible to infections.
Adenovirus: Adenovirus is a type of DNA virus that commonly causes respiratory, eye, and gastrointestinal infections. It is also used as a vector in gene therapy due to its ability to deliver genes to host cells.
Adenoviruses: Adenoviruses are a group of DNA viruses that can infect a variety of host cells, including those in the respiratory tract. They are commonly associated with respiratory illnesses and have also been utilized in the development of gene therapy techniques.
Alzheimer's: Alzheimer's is a progressive neurodegenerative disorder that primarily affects the brain, leading to cognitive decline, memory loss, and impaired thinking and reasoning abilities. It is the most common form of dementia, characterized by the gradual destruction of brain cells and the disruption of neural connections, ultimately impairing an individual's ability to perform everyday tasks.
Center for Drug Evaluation and Research (CDER): The Center for Drug Evaluation and Research (CDER) is a branch of the FDA responsible for ensuring that drugs marketed in the U.S. are safe and effective. CDER evaluates new drugs before they can be sold and monitors existing drugs to ensure ongoing safety.
CRISPR-Cas9: CRISPR-Cas9 is a gene-editing technology that uses a guide RNA and the Cas9 enzyme to precisely target and modify specific DNA sequences within a genome. It has revolutionized genetic engineering and has widespread applications in fields like microbiology, pharmaceuticals, and gene therapy.
Cystic fibrosis: Cystic fibrosis (CF) is a genetic disorder that affects the respiratory and digestive systems, caused by mutations in the CFTR gene. It leads to thick, sticky mucus production, which obstructs airways and promotes bacterial infections.
Cystic Fibrosis: Cystic fibrosis is a genetic disorder that primarily affects the lungs and digestive system. It is caused by a mutation in the CFTR gene, which is responsible for regulating the movement of salt and water in and out of cells. This mutation leads to the production of thick, sticky mucus that can clog the airways and various organs, leading to a range of severe health complications.
Ex Vivo Gene Therapy: Ex vivo gene therapy is a therapeutic approach where cells are removed from the patient's body, genetically modified, and then reintroduced back into the patient. This allows for targeted genetic modifications to be made outside the body before delivering the altered cells to treat a specific disease or condition.
Food and Drug Administration: The Food and Drug Administration (FDA) is a U.S. federal agency responsible for regulating food, drugs, medical devices, and biological products. It ensures the safety, efficacy, and security of these products to protect public health.
Gelsinger: Jesse Gelsinger was the first person publicly identified as having died in a clinical trial for gene therapy. His case significantly impacted the field of gene therapy, leading to increased scrutiny and regulatory changes.
Gene therapy: Gene therapy is a medical technique that modifies genes to treat or prevent disease. It often involves inserting, altering, or removing genes within an individual's cells using vectors like viruses.
Gene Therapy: Gene therapy is a technique that uses genes to treat or prevent disease. It involves the introduction of genetic material into cells to compensate for abnormal genes or to create a beneficial genetic effect, such as fighting disease. Gene therapy has the potential to treat a wide range of genetic and acquired diseases by targeting the underlying genetic causes.
Genome Editing: Genome editing, also known as gene editing, is a powerful technology that allows for precise and targeted modifications of an organism's genetic material. This technique enables the addition, removal, or alteration of specific DNA sequences within a genome, offering the potential to treat genetic disorders, enhance desired traits, and even create novel organisms.
Germ-line gene therapy: Germ-line gene therapy involves modifying the genes in germ cells (sperm or eggs) to correct genetic defects that can be passed on to future generations. It aims to treat or prevent disease at the earliest possible stage, before an embryo develops.
Germ-line Gene Therapy: Germ-line gene therapy is a type of genetic intervention that targets the reproductive cells, such as sperm or eggs, in order to modify the genes that are passed on to future generations. This approach aims to correct or prevent inherited genetic disorders by making permanent, heritable changes to the genome.
Hemophilia: Hemophilia is a rare genetic disorder characterized by the body's inability to properly clot blood, leading to excessive and uncontrolled bleeding. This condition is primarily caused by a deficiency or dysfunction of certain blood clotting factors, which are essential for the normal coagulation process.
Immunotherapy: Immunotherapy is a type of treatment that harnesses the power of the body's own immune system to fight diseases, particularly cancer. It works by stimulating or modifying the immune system to recognize and attack abnormal cells more effectively.
In Vivo Gene Therapy: In vivo gene therapy is a type of genetic therapy where therapeutic genes are directly delivered into the patient's body to treat a genetic disorder or disease. This approach aims to address the underlying genetic cause of a condition by introducing functional genes or modifying existing genes within the patient's cells.
Informed consent: Informed consent is the process by which a patient or participant voluntarily confirms their willingness to participate in a particular procedure, after being informed of all the potential risks, benefits, and alternatives. It is essential for ethical practices in clinical research and medical treatments.
Insertional Mutagenesis: Insertional mutagenesis is a type of genetic mutation that occurs when a foreign DNA sequence is inserted into a gene or regulatory region, disrupting the normal function of the affected genetic element. This process is particularly relevant in the context of gene therapy, as it can have significant implications for the safety and efficacy of genetic interventions.
Institute of Medicine: The Institute of Medicine (IOM), now known as the National Academy of Medicine, is a nonprofit organization that provides expert advice on issues relating to health and science policy. It plays a critical role in shaping public understanding and policies related to healthcare and medical research.
Investigational New Drug (IND) application: An Investigational New Drug (IND) application is a request submitted to the FDA to obtain permission to start human clinical trials for a new drug. This application includes data from preclinical studies to ensure the drug's safety and efficacy.
Leukemia: Leukemia is a type of cancer that affects the blood and bone marrow, characterized by the uncontrolled production of abnormal white blood cells. It is a hematological malignancy that can significantly impact the body's ability to fight infection and maintain healthy blood cell levels.
Liposomes: Liposomes are microscopic, spherical vesicles composed of a lipid bilayer membrane that can be used as a drug delivery system. They are designed to encapsulate and transport various therapeutic agents, including drugs, genes, and other biomolecules, to targeted sites within the body.
Lymphoma: Lymphoma is a type of cancer that originates in the lymphatic system, which is part of the body's immune system. It is characterized by the abnormal growth and proliferation of lymphocytes, a type of white blood cell, leading to the formation of tumors in the lymph nodes, spleen, bone marrow, and other parts of the body.
National Academy of Medicine: The National Academy of Medicine (NAM) is an American non-profit organization that provides expert advice on health and medical issues. It aims to improve health by advancing science, accelerating health equity, and providing independent, authoritative information.
National Institutes of Health: The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It supports and conducts scientific studies to improve health and save lives.
New Drug Application (NDA): A New Drug Application (NDA) is a regulatory submission to the U.S. Food and Drug Administration (FDA) for approval to market a new pharmaceutical for sale and use. It includes data on the drug's safety, efficacy, and manufacturing processes.
Off-Target Effects: Off-target effects refer to the unintended or undesirable consequences that can occur when a therapeutic intervention, such as gene therapy, interacts with biological targets other than the intended target. These effects can lead to adverse reactions or unexpected outcomes that were not the primary goal of the treatment.
Office of Human Research Protection: The Office of Human Research Protection (OHRP) is a U.S. government agency responsible for ensuring the ethical conduct and protection of human subjects in research. OHRP provides guidance, oversight, and education to institutions conducting research involving human participants.
Ornithine transcarbamylase (OTC) deficiency: Ornithine transcarbamylase (OTC) deficiency is a genetic disorder characterized by a lack of the enzyme OTC, which plays a crucial role in the urea cycle. This deficiency leads to an accumulation of ammonia in the blood, causing hyperammonemia.
Parkinson's: Parkinson's is a chronic and progressive neurological disorder that primarily affects the motor system. It is characterized by the gradual loss of dopamine-producing neurons in the brain, leading to a range of motor and non-motor symptoms. This key term is particularly relevant in the context of gene therapy, as researchers are exploring ways to use genetic interventions to treat the underlying causes of Parkinson's disease.
Recombinant DNA Advisory Committee: The Recombinant DNA Advisory Committee (RAC) is a group that provides guidance on research involving recombinant DNA, including the ethical and safety considerations. It plays a crucial role in ensuring that gene therapy and other genetic research are conducted responsibly.
Retroviruses: Retroviruses are a unique class of viruses that use RNA as their genetic material and employ a reverse transcriptase enzyme to convert their RNA into DNA, which is then integrated into the host cell's genome. This distinctive life cycle and genetic structure allows retroviruses to persistently infect their hosts and utilize the cellular machinery for their own replication.
Risks: Risks in gene therapy refer to the potential adverse effects and uncertainties associated with the use of genetic techniques to treat diseases. They can include unintended genetic modifications, immune reactions, and ethical concerns.
SCID: SCID (Severe Combined Immunodeficiency) is a primary immunodeficiency disorder characterized by the disturbed development of functional T cells and B cells. It results in severe, life-threatening infections due to an extremely compromised immune system.
Sickle Cell Anemia: Sickle cell anemia is an inherited blood disorder characterized by abnormal hemoglobin, which causes red blood cells to become sickle or crescent-shaped. This genetic mutation affects the delivery of oxygen throughout the body, leading to a range of complications and health issues.
Somatic-cell gene therapy: Somatic-cell gene therapy involves the insertion, alteration, or removal of genes within the somatic cells of a patient to treat or prevent disease. It does not affect the patient's germline and therefore is not passed on to future generations.
Somatic-Cell Gene Therapy: Somatic-cell gene therapy is a form of genetic engineering that involves the introduction of genetic material into the non-reproductive cells of an individual to treat a specific disease or disorder. It aims to correct genetic defects or enhance the function of targeted cells, without affecting the individual's germline cells or future offspring.
Transgene: A transgene is a gene that has been artificially inserted into the genome of an organism, often from a different species, to introduce a new trait or characteristic. Transgenes are a fundamental component of genetic engineering and play a crucial role in the field of gene therapy.
Viral Vectors: Viral vectors are modified viruses that are used as vehicles to deliver genetic material, such as DNA or RNA, into target cells. These engineered viruses are designed to infect cells and introduce the desired genetic information without causing the original viral disease.