Viruses are small particles that are so tiny they cannot be seen by a regular light microscope. However, viruses can be found almost anywhere you look. Viruses specialize in carrying genetic material into all kinds of cells, including human cells. Many viruses are harmless to humans while others can cause illnesses like the cold, the flu, or COVID-19. Recently, scientists have been using viruses to deliver genes into cells to cure human diseases! This is called gene therapy. Genes are the blueprints for the proteins that make up the human body, and mistakes in a gene can cause disease. Gene therapy is a way to treat these types of diseases. To create a gene therapy, scientists cut out a virus’s genes and replace them with properly working human genes. These modified viruses can then be used to deliver healthy genes and treat disease.
What Are Viruses?
Viruses are found everywhere—they exist on your skin, in your gut, and on surfaces all around you. There are about 100 times more viruses in your body than human cells . Of the many different kinds of viruses that exist, most are harmless and exist peacefully within living organisms. There are over 140,000 different kinds of viruses found in the healthy human gut alone . Most of the viruses that you have heard of, however, cause illnesses like the flu or COVID-19. Even the common cold is often caused by a family of viruses called rhinoviruses.
A virus is a tiny particle made of a protein shell, containing its own genetic material (Figure 1A). A virus’s main purpose is to make more copies of itself, and it does this by hijacking a cell, delivering its genetic material into the cell, and forcing the cell to create virus copies (Figure 1B). DNA is the genetic material that contains the instructions, like a set of blueprints, for how to make all the proteins in the body. Proteins are complex molecules, and different proteins have different purposes and functions, including making up the shell of a virus or carrying out important work inside a cell. Sections of the DNA that contain the instructions for how to make individual proteins are called genes.
Although a virus has its own genetic material, it does not have the proper machinery for reading genes and creating its own proteins. This is why viruses must infect cells—they rely on the protein factories inside the cells they infect. The human cell has a hard time telling its own genes apart from a virus’s genes, so the cell mistakenly reads the virus’s genes and produces viral proteins along with human proteins. That is why viruses are not considered living organisms—they cannot multiply on their own, without infecting a cell.
After a virus multiplies inside a cell, newly made viruses are released from the cell and can infect neighboring cells. As we mentioned, this process can lead to contagious diseases like COVID-19 but, in the past few decades, scientists have been harnessing the gene-delivery power of viruses to treat and cure diseases.
What Is Gene Therapy?
Genetic disorders are diseases that occur when there is a mistake called a mutation in a person’s DNA. Because DNA contains the instructions for building proteins, mutations can lead to the loss of a protein that is important for a body function or even for survival.
About 50 years ago, scientists had an interesting idea: what if we could transfer healthy genes into the cells of people who suffer from a genetic disease ? Treating disease by transferring genetic material into cells is called gene therapy. Scientists also thought that maybe we could use viruses to insert a healthy gene into cells. Maybe the viruses could “trick” cells into producing the healthy, functional protein they are missing. A few decades later, scientists achieved just that (Figure 2)! To use viruses for gene therapy, scientists replace viral genes with a corrected version of the mutated human gene. They then inject these modified viruses into the part of the body where the protein should be found. There, the modified virus enter human cells and release healthy copies of the gene. The cells can then read this corrected gene and build a functional protein. Removing the viral genes makes gene therapy viruses unable to replicate, so they can no longer spread from cell to cell.
An Example Of Gene Therapy
One of the first diseases to be treated using gene therapy is called Leber congenital amaurosis (LCA). LCA causes blindness as a result of mutations in the gene coding for a protein necessary for vision. The retina is the part of the eye that detects light. It is located at the back of the eye and it is made up of several types of cells. In healthy eyes, cells called retinal pigment epithelial (RPE) cells have a gene that codes for a protein called RPE65, which allows for normal vision (Figure 3A). When there are mutations in the RPE65 gene, the protein loses its function, which causes the retinal cells to die—leading to blindness (Figure 3B). Scientists can modify a virus by replacing virus genes with a healthy RPE65 gene. These virus particles are then loaded into a syringe and injected into the eyes of patients with LCA. The modified virus enters RPE cells and deliver the healthy gene, so that the RPE cells can produce functioning RPE65 proteins. This allows the retinal cells to start working properly (Figure 3C). While vision is not completely restored using the currently available gene therapy, patients have experienced improvement in their ability to see .
Although gene therapy has shown promising results in diseases like LCA, doctors and scientists still face several challenges to making gene therapy work perfectly. Currently available treatments are not yet fully effective. To cure inherited diseases, scientists will need to improve the delivery of gene therapy, so that every diseased cell receives a healthy gene—something that is not currently achievable. Scientists will also need to find ways to undo any previous damage to the tissue that happened as a result of the disease, because gene therapy cannot bring back cells that have already died—it can only prevent more damage from happening. Finally, the use of viruses to deliver therapeutic genes can sometimes cause unwanted side effects, such as an immune response in which the body tries to attack the viruses as foreign intruders.
Gene therapy also raises many unique ethical concerns, because it involves making permanent changes to human DNA. Once a gene therapy is given, the changes cannot be undone, and they could last for a lifetime. Because gene therapies are so new, unexpected things may happen when gene therapies are given to patients. Because of the risk of unintended consequences, doctors are still only using gene therapies with great caution. Lastly, because they are so new and currently expensive, gene therapy treatments are not widely available to all patients. Creating fair and affordable access to gene therapies is an important goal. Scientists are working to make patients’ lives better by developing new ways to deliver genes and produce healthy proteins.
In this article, we described the basics of gene therapy for the treatment of inherited diseases. Researchers have long studied how viruses can hijack human cells by injecting their own genetic material and forcing human cells to produce viral proteins. Using this knowledge, scientists have been developing gene therapies by cutting out a virus’s own genes and replacing them with healthy human genes. This way, we can use a virus’s natural ability to infect cells to replace unhealthy genes in patients who suffer from genetic diseases. While the method is not perfect, scientists are working hard to improve gene therapy in the hopes of one day being able to cure devastating genetic disorders affecting the eyes, heart, blood, and much more.
Genetic Material: ↑ The “blueprints” cells (and viruses) use for making proteins. DNA and RNA are the genetic materials in human cells and in viruses.
Genes: ↑ The instructions for making proteins.
Mutation: ↑ A change in DNA that can cause disease.
Gene Therapy: ↑ Treating disease by transferring genetic material into cells.
Retina: ↑ A light-sensitive, multilayer tissue, found inside the eye and responsible for vision.
Retinal Pigment Epithelial Cells: ↑ Cells in the retina that are necessary for the health of the retina and normal vision.
Ethical: ↑ Ethical means making decisions based on what is right and just, and following principles and values that guide us to treat others with respect and fairness.
Conflict of Interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
 ↑ Mokili, J. L., Rohwer, F., and Dutilh, B. E. 2012. Metagenomics and future perspectives in virus discovery. Curr. Opin. Virol. 2:63–77. doi: 10.1016/j.coviro.2011.12.004
 ↑ Camarillo-Guerrero, L. F., Almeida, A., Rangel-Pineros, G., Finn, R. D., and Lawley, T.D. 2021. Massive expansion of human gut bacteriophage diversity. Cell 184:1098–109 e9. doi: 10.1016/j.cell.2021.01.029
 ↑ Friedmann, T., and Roblin, R. 1972. Gene therapy for human genetic disease? Science 175:949–55. doi: 10.1126/science.175.4025.949
 ↑ Wang, X., Yu, C., Tzekov, R. T., Zhu, Y., and Li, W. 2020. The effect of human gene therapy for RPE65-associated Leber’s congenital amaurosis on visual function: a systematic review and meta-analysis. Orphanet. J. Rare Dis. 15:49. doi: 10.1186/s13023-020-1304-1