Gene therapy, a cutting-edge medical approach, modifies genes to treat or cure diseases, including AIDS, cancer, cystic fibrosis, diabetes, and heart disease.
By being able to knock out/in and replace genes, gene therapy can rectify the existing genetic disorders in the patient by altering the gene expression.
While the idea of gene therapy began as early as in the 1960s, the first successful gene therapy was done in 1990 for severe combined immunodeficiency (SCID). Since then, gene therapies have evolved manifolds, where gene editing is a possibility instead of just replacement.
At Infinix Bio, we support the continued development of gene therapy: a biotechnology that will change the world of medicine.
Source: Boston Children’s Hospital
The important mechanisms of gene therapy are the various delivery methods, targeting strategies, and action mechanisms.
Before we break down the processes of gene therapy, learn more about our pre-clinical services.
The main step of gene therapy is introducing the altered genetic material into the cells, using vectors which carry the gene to the target location.
Gene-editing tools include CRISPR-Cas9, TALENs, and zinc-finger nucleases. These technologies involve modified RNA and enzymes that alter, remove, or add genetic material in the cell’s genome.
Below are two types of vectors that are commonly used in gene therapy:
Sources: National Library of Medicine, MedlinePlus
To accurately deliver and control the vectors carrying the modified gene, different targeting effects are used, such as:
There are several biochemical mechanisms by which the modified genes excerpt their intended effects on the targeted cells, including:
Source: FDA
Majority of the gene therapy treatments are still in the clinical trial and developmental phases. At present, FDA approved gene therapy based treatment for Leber congenital amaurosis, which is a genetic disorder that causes blindness, is available.
Eventually, with the advancement in the field, gene therapy could help in treating inherited genetic disorders like cystic fibrosis, hemophilia, and sickle cell anemia.
Different approaches such as gene replacement, silencing, and editing can be used to correct the genetic mutations that lead to the onset of diseases. By targeting the specific cells that contain the genetic mutations, these approaches can edit the existing genes or introduce completely new and healthy genes. A big challenge with gene therapy is the introduction of the new gene/vector might elicit the patient’s immune system and make the treatment less effective.
Because gene therapy is a newly emerging and evolving science , there are a lot of challenges and limitations, many of which require more indepth research and development. When it comes to rare genetic disorders, due to the limited funding availability, the reach of gene therapy based treatment development is limited.
Sources: Learn.Genetics, National Heart, Lung, and Blood Institute
Cancer is recently added to the list of diseases being tested for gene therapy treatment, and ongoing research looks promising.
Here are some of the treatment strategies:
As a contract research organization, at Infinix Bio we support the pre-clinical and clinical studies focused on gene therapy and immunogenicity.
Sources: National Library of Medicine, National Library of Medicine
One of the most appealing attributes of gene therapy is its promise to provide a long-term or permanent cure for many diseases. This is encouraging in terms of neurodegenerative diseases as the central nervous system (CNS) related conditions are particularly difficult to treat due the blood-brain barrier factor .
The blood-brain barrier restricts the passage of large molecules, but the engineered viral vectors carrying the modified genes are able to cross this barrier and reach the affected neurons. Nonparticles are also being explored as an alternative vector for treating neurological disorders.
Irrespective of the vector being used to cross the blood-brain barrier, precision targeting of brain regions is a high priority factor to maximize the therapy. Gene promoters can also help to ensure that the delivered genes are well expressed in the diseased neurons
Upon introducing functional genes into neurons, normal neuronal function can be promoted and disease progression can be counteracted.
Source: National Library of Medicine
Gene therapy can be used to provide effective treatment for autoimmune diseases and immunodeficiency disorders. The immune cells from the patient once collected can be altered by introducing a healthy version of the affected gene to enhance the immune system.
This therapy is currently being tested on individuals who suffer from autoimmune diseases like lupus and severe combined immunodeficiency (SCID).
There are some limitations such as:
Sources: Guardian, Immune Deficiency Foundation
There are countless ongoing clinical trials for gene therapy treatments. Some of the diseases these target include:
Clinical trials are extremely important in making any progress in biotechnology, and medicine in general. But, there are certain considerations, both on a regulatory and ethical level, that clinical trials must undergo.
Let’s delve more into clinical trials for gene therapy.
Before the clinical trial starts, preclinical studies must be done . These studies test the treatments on cells and animals to determine their effectiveness and side effects.
Then, the data and clinical trial design are submitted to the FDA to assess risk and approve the trial. For clinical trials, patient’s selection is based upon determined criteria, such as age, gender, medical history, specific gene variants, etc.
Clinical trials are conducted in different stages, usually four, but many gene therapy trials are structured as a phase I / II study, where a small group of participants are tested for the safety and efficacy of the treatment . This also helps in making the entire process more efficient and quick as typically the clinical trials take a long time. Then the trial will expand the number of participants to ensure universal treatment abilities. Phase four is the most important and critical part of the clinical trial especially when the product is undergoing a final market approval.
Finally, once the treatment is analyzed, examined and approved by the FDA it becomes available to all patients.
Source: American Society of Gene and Cell Therapy
The main regulatory agencies overseeing gene therapy development and approval are the government administrations. In America, this agency is the U.S. Food and Drug Administration (FDA).
Preclinical data, which is submitted for approval, must include the mechanism of action, safety, efficacy, toxicology, and pharmacology. The preclinical studies are done in animal and cell studies.
When manufacturing the drug, scientists must adhere to specific good manufacturing practice (GMP) standards, that are enforced by the FDA and World Health Organization.
To gain approval, scientists must submit an Investigational New Drug (IND) application to the FDA. This application outlines the drug’s:
After submitting the IND, it takes 30 days for the FDA to approve the form, where they assess the amount of risk participants will face.
Source: FDA, WHO, American Society of Gene and Cell Therapy
Phase four of all clinical trials involves repeat testing and follow-up appointments that monitor safety and efficacy of gene therapy treatment participants.
If adverse symptoms or conditions are observed in the patients, the researchers must report this to the FDA as well as consumers.
Pharmacovigilance, is a science that is dedicated to detecting and preventing long-term drug effects to ensure patient safety.
As the medical world continues to advance, new gene therapy research constantly emerges.
Researchers are working collaboratively to quickly address the problems of vector toxicity and immune attacks, increasingly advancing research and expanding access.
Gene editing has grown through technological advancements, such as CRISPR-Cas9. These innovations enhance precision and efficiency, allowing for the ability to edit the genes responsible for the disease onset with the new and healthy ones.
Viral and non-viral vectors are constantly being improved for better safety, efficiency, and target-specification. Vectors like adeno-associated virus (AAV) variants and nanoparticles are currently being explored and tested for their future potential.
Synthetic biology has also been integrated as a strong tool into gene therapy allowing for more patient customization and increased functionality.
Source: Boston Children’s Hospital
The scope of diseases that gene therapy can treat has advanced to include more common cardiovascular diseases and diabetes. Many diseases have underlying genetic factors, so gene therapy can target those specific genes.
Some challenges come with gene therapy, including:
As a newly emerging form of treatment, gene therapy is constantly undergoing development to enhance the safety , minimizing the off-target delivery of vectors and immune responses that kill the incoming genes before they can be effective.
There are also ongoing ethical dilemmas, as some are concerned about the effects of germline editing and unintended consequences.
Gene therapy can change the medical landscape as we know it, treating many diseases and improving patient outcomes.
But, continued research, clinical development, and regulatory oversight are essential to realize the full potential of gene therapy.
With research development ,collaboration among scientists, clinicians, regulators, and stakeholders is becoming more critical to address challenges and ensure the safe and effective translation of gene therapy into clinical practice.
Learn more about Infinix Bio’s pre-clinical services and reach out with any questions.
What is gene therapy?
Gene therapy is a medical technology that allows for the addition, removal, or editing of disease-causing genes .
How does gene therapy work?
Gene therapy works by entering the body on viral or non-viral vectors that contain the new gene or gene editing products, then finding the affected cells, impacting them and eliminating or silencing the gene expression that causes the disorder.
What diseases does gene therapy treat?
Gene therapy is currently being tested to treat many diseases, including genetic disorders, cancer, neurological disorders, and immune diseases.
What are the limitations of gene therapy?
Gene therapy can be an extremely expensive treatment option and it is not easily scaled to treat a large group of people. The body’s immune system also tends to attack vectors, treating them like infections, which limits the effectiveness.
Our experienced lab team is here to help. Reach out today to learn more.
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