Basic research exploring human and nonhuman genomes is critical to help scientists understand the basic biology underlying disease, as well as to discover new possible therapeutic targets. Genome editing is currently being applied to research on cancer, mental health, rare diseases, and many other disease areas. Although excitement about the potential for gene therapy has grown tremendously since the discovery of CRISPR, the vast majority of work undertaken by scientists funded by NHGRI or other NIH Institutes takes place in the petri dish and in nonhuman organisms such as mice or zebrafish. Researchers rely on genome editing tools as a way to explore the connection between genotype (genes) and phenotype (traits). A typical study might be to model human disease in mice by deleting or editing certain genes that are thought to contribute to the disease. This approach can help researchers determine if specific changes made to the genome contribute to the disease. It can also lead to the creation of "disease models," or laboratory animals that mimic human diseases and can be studied to test new therapies.
In the clinic, there are proposals to use genome editing as a treatment for disease. Many diseases from cancer to asthma have genetic bases. Through the application of genome editing technologies, physicians might eventually be able to prescribe targeted gene therapy to make corrections to patient genomes and prevent, stop, or reverse disease.
There are two different categories of gene therapies: germline therapy and somatic therapy. Germline therapies can alter many cell types but by definition they also change genes in reproductive cells (like sperm and eggs). These changes would then be passed down from generation to generation. Germline therapy could potentially prevent inheritance of diseases. Somatic therapies, on the other hand, target non-reproductive cells. Changes made in these cells affect only the person who receives the gene therapy and do not pass on to future generations. Somatic therapies could be used to slow or reverse the disease process.
Of the two types of gene therapy, somatic therapies are the less controversial, and therapies using this approach are under development in research and commercial labs around the world. Treatments for HIV and cancer are being tested in clinical trials in patients. In contrast, germline therapies pose a greater number of ethical hurdles because of their ability to affect future generations. Critics have highlighted the possibility that germline therapies would pave the way for genetic enhancement, the use of genome editing to change non-medically relevant characteristics, such as athletic ability or height. More information about the ethical concerns around genome editing can be found at: What are the ethical concerns about genome editing?
Ethical concerns aside, there are still significant technical barriers that prevent genome editing therapies from entering the clinic. The research and regulatory communities have yet to begin evaluating the safety of potential treatments. The risk of off-target edits, or unintended edits, and their effects are still unknown, even for a technology like CRISPR that is many times more precise than previous techniques. Another problem to overcome is how to deliver the genome editing therapy to the right cells in the body in an effective manner.
One other challenge for gene therapy is that there is still much to learn about which genes are involved in most diseases and how different changes in these genes affect a person's risk of getting a disease. Many genes have more than one function, and in some cases editing a gene to "cure" one disease could create another. Scientists are also working to learn more about how genetic changes and environmental influences combine to result in disease and how genes interact with each other. Additionally, scientists need to learn more about how genes are controlled and how variants in these "controlling" regions of the genome are associated with disease risk. In the case of common diseases, such as diabetes, many genetic changes and environmental influences combine to result in disease. Therefore, scientists need to learn more about these changes before many gene therapies can be developed.
Posted: August 3, 2017