Here’s a guide to some of the key terms and what they mean.
Biomedical research is a field of science that aims to understand biological processes with the goal of curing or treating disease in humans and animals. Biomedical research includes both basic research and clinical research. The difference is that basic research is done in a lab, and clinical research is conducted with patients. Understanding how living things operate on their most basic level can give us clues to achieve better health.
Genetic material typically means DNA and RNA. DNA and RNA are strings of molecules that help instruct cells to create proteins. DNA helps store the genetic information, like a blueprint. RNA’s function is to convert the genetic instructions contained within DNA into a format that helps cells build the correct proteins.
Gene therapy is the introduction, removal or change in genetic material in the cells of a patient to treat an inherited or developed disease. Typically, genetic material, such as a working copy of a gene, is transferred into the target cell using a vector. A vector is often a virus, but the viral genes that could cause disease are removed. Once in the cell, a working copy of the gene will help make functioning proteins despite the presence of a faulty gene. Achieving the normal expression and function of proteins makes a big impact on our overall health.
Cell-based gene therapy is the transfer of cells into a patient with the goal of improving a disease. Some cell therapies are now routine, like blood transfusions.
One approach is gene-modified cell therapy, referred to as ex-vivo gene therapy, which removes the cells from the body and then a new gene can be introduced or a faulty gene can be corrected. The modified cells are then put back into the body. An example of this approach is CAR-T cell-based gene therapy. A patient’s T cells, which are a kind of immune cell, are changed in a lab by using a vector to add a gene that changes cells in a way that enables them to recognise and attack cancer cells.
Gene editing is another therapeutic approach generating a lot of interest. The goal of gene editing is to remove, disrupt or correct faulty elements of DNA within the gene rather than replace the gene as regular gene therapy would. Gene editing uses systems that are highly precise to make this change inside the cell. The cells can be from the patient or donor. There are no approved gene editing treatments yet, but many are currently being researched in clinical trials.
Gene and cell-based gene therapy vs. traditional medicines
With all the talk about these different approaches, you might be wondering where traditional prescription medicines come into play. These medicines are typically used to manage diseases, mitigate symptoms and relieve pain. The concept behind gene and cell-based gene therapy is to target the exact cause of the disease, so that the person should no longer have recurring symptoms, ideally after a single treatment. For example, gene therapy is done by adding working genes within specific cells. You can’t deliver a gene through a pill or inhalation, so the therapies cannot be applied with a standard type of drug that is available at a pharmacy. Instead, you will find approved gene therapies at specific treatment centres.
Gene therapies are not only different from other treatments available, but they aim to treat diseases with no treatments currently available or in some cases the treatment options available don't work well, can be high risk and don't offer the possibility of a cure. Many of the diseases for which gene therapy offers promises to treat are rare inherited disorders. Of the 6,000 rare diseases that exist, 95% have no approved current treatment.
It is worth noting that gene therapy targets somatic cells which are the vast majority of cells in the body but are not our reproductive or germline cells. This means that the treatment is corrective to the patient only and would not be passed along to the next generation. Although there is plenty of promise in these approaches, they can’t be viewed as a wonder cure-all. Like any medical treatment, they present their own unique challenges and benefits.
Challenges and benefits
Some genetic diseases are caused by mutations in a single gene, while others are a result of mutations in multiple genes, for example, cancer. Additionally, environmental factors, such as UV radiation from the sun, can play a role in causing disease and determining severity. Working with rare diseases yields a very small number of patients with one specific genetic defect which requires development of a specific gene therapy approach for each. The complexity of these disease characteristics creates variables in developing and testing potential treatments. Currently our gene and cell therapy options are limited to treating only the diseases that are caused by a single gene mutation.
Funding and regulatory issues
Testing treatments in clinical trials remains a huge challenge as it requires funding for the studies, preparation of regulatory documents and preparing materials suitable for humans. There is a lot of cost that goes into the extra work it takes to understand the disease and ensure these interventions are safe for the patients.
Right place, right time
Therapies need to express the gene in the right tissue, at the right level, for the right amount of time. This means that a lot of research goes into identifying the best means of delivering the genetic material. Furthermore, the response of the patient’s immune system also needs to be considered based on the therapy.
Testing and durability of treatment
Typically, there is only a small number of patients with the rare disease who are eligible to take part in the clinical trial, even if it is expected that in the future gene therapies will be investigated also for more prevalent diseases. Since the majority of gene and cell-based gene therapies in development today are considered investigational, meaning they are currently being researched and developed in clinical trials, their long-term effects are still in question. When the gene therapy reaches the registration stage and becomes a commercial product, the European Medicines Agency (EMA) is still requesting post-approval, long-term monitoring of safety and efficacy.
Ready for the rare
Gene and cell-base gene therapy can help treat rare and debilitating diseases that have limited treatment options. Often, these rare inherited diseases would otherwise end in disability or premature death. With gene and cell-based gene therapy, early studies have already shown that the progression of these rare diseases has been slowed or completely stopped.
One significant advantage of gene therapy over traditional pharmacological approaches is that therapeutic benefits may potentially be maintained over a long period of time without the need of repeated interventions. A fundamental aspect of gene therapies is that they aim to treat the cause of the disease, not just the symptoms.
It’s difficult to design specific medicines that influence specific proteins. However, with gene therapy it may be possible to design therapeutic agents that can influence any of our body’s roughly 20,000 genes.
Last updated: 27 May 2021
This content was adapted from the American Society of Gene and Cell Therapy Patient Information Program