Would you believe it's been happening for years now? While we're far from curing all genetic diseases, we've already made strides in humans to correct the genetic code to alter or reverse disease course. It all relies on the gene editing technique called CRISPR.

Basically, CRISPR is a system that can target specific gene sequences within a person's genome, and precisely edit those targets to change their genetic code based on provided instructions. The system is also small enough that once it's designed by scientists, it can be loaded into a virus, which can then replicate itself and the system enough so that a bunch of cells can be edited. These viruses are altered so that they can inject DNA and the CRISPR machinery into human cells but don't cause any infection. Many treatments have been developed that revolve around extracting human cells with genetic diseases, altering them in the lab to fix the mutation, then injecting those cells back into people. For instance, sickle cell disease, a debilitating disease that affects red blood cells, has been essentially cured in patients using this technique (link to podcast story below). This only works however if the healthy cells made in the lab can be put back in and replace the unhealthy cells that the person has. Not all human genetic diseases can be treated like this.

However, newer treatments have been developed that can actually alter human genetic code in the body, by injecting the viruses (again, these viruses are harmless) with the CRISPR machinery into the person. Two such approaches have been tried that I'm aware of, and at least one of them shows very promising results (links below), however both of these are still newer techniques and being studied and verified for efficacy and safety in clinical trials. However, it does underline the fact that we already possess the technology to address genetic diseases at their source and provide treatments and even cure for these often debilitating and life long illnesses. Eventually we'd ideally be able to address these genetic diseases even earlier by using CRISPR in the early embryo, however gene editing such as this carries with it a wealth of ethical concerns if it is taken beyond merely correcting genetic diseases.

Genetic disease treatment.

We already can do that! At least for a few diseases. Gene therapy (in its current state) is typically used for treating genetic disorders. These types of disorders occur when a patient’s DNA has some sort of mutation in its sequence that causes the cells to either not generate a necessary protein or generate slight variations on the protein that negatively impact its function. For example, people with sickle cell anemia have a single DNA mutation where one adenine nucleotide is replace with a thymine. This small change slightly shifts the behavior of the hemoglobin proteins in their blood, which in turn changes the shape of their blood cells.

Gene therapy works by injecting a healthy set of DNA into a patients cells. This healthy DNA enters the cell nucleus where it can replace the mutated DNA, curing the disorder. Replication of the healthy DNA during cell replication then propagates this treatment throughout the body (or a localized region of the body), leading to a permanent cure.

Currently, only 6 types of gene therapy treatments have been approved in the US, mostly aimed at treating a handful of specific types of cancers. But this is a very active research field with several exciting new therapies in development and undergoing clinical trials. The process of medical treatment trials and approval is slow, so it may be several years before these new technologies are on the market (if they get approved). In addition to treating genetic disorders, gene therapy is also being adapted to treat viral infections (e.g. HIV) and drug-resistant bacterial infections. In these cases, instead of supplying healthy DNA to human cells, the gene therapy aims to sabotage the genetic code of the trespassing viruses and bacteria.

Research is also constantly being done to improve the technologies used in order to increase effectiveness, gene-editing accuracy, and safety of these treatments. Developments in CRISPR-Cas gene-editing systems are a particularly promising technology that will only further accelerate these treatments.

As for preventing diseases, we sort of have that too! The Pfizer and Moderna vaccines for COVID-19 are both mRNA vaccines. These work by injecting a small fragment of the genetic code of the COVID-19 virus into a patient’s cells. The patient’s cells then use these fragments of RNA to build pieces of the virus that the immune system can detect and build immunity for, preventing future infection. While not technically “gene therapy” since these do not manipulate a person’s genetic code or have any permanent impact, they are a cool piece of technology demonstrating the utility of DNA/RNA treatments in medicine!

Scientists can do some gene therapy now. For example, there’s a type of blindness caused by a mutation. It is now possible to inject “good copies” of that gene into the eye of people with the mutation and help them see. Check out this video that explains it:

The process of developing gene therapies is difficult. Even after researchers figure out which gene is the problem, they have to have a way to safely and effectively introduce the normal gene into the person’s cells. All of your cells (except for mature red blood cells and gametes) have a complete set of your DNA, but each cell only uses certain genes. For example, if a person has a genetic disorder that doesn’t let their liver make an important enzyme, the genes just have to go to the person’s liver cells. Delivering the repaired cells to the liver can be a challenge.

One of the most important breakthroughs in gene therapy is the development of CRISPR-cas 9 technology that helps scientists and doctors edit DNA. This process has a lot of potential to help people with many different genetic disorders. This video explains how it works:

Gene therapy and genetic disorders.

If you could choose one disease to cure, which would you choose?

We're in the middle of doing trials and safety testing for gene editing as we speak! In 2019, Editas Medicine, a biotechnology company, and Allergan, a pharmaceutical company, announced that they were enrolling patients in one of the first tests in the US whether the gene-editing technology, CRISPR, can directly fix mutations found in eye cells in a human body.

Another recent clinical trial that tested the safety of CRISPR gene editing is being held by Intellia Therapeutics and Regeneron Pharmaceuticals to reduce the amount of toxic protein build-upin patients with Familial Transthyretic Amyloidosis. Their Phase I study (safety trials) showed that delivering and editing cells in human livers is possible. In this particular case, you also do not need to edit all of the liver cells to get therapeutic benefits.

There are still challenges that remain: many scientists are interested in using gene editing in brain disorders like Huntington's Disease. However, the brain is one of the most difficult organs to target because it has so many protections to prevent random substances from reaching it, most important of which is called the blood brain barrier. Also, unlike the liver, which only needs to have part of its cells edited, you need to edit every neuron in the brain that you want to save.

In the end, I think the answer is, the day may be closer than you think, but will require more safety trials before we put it into practice.

1. Crispr gene editing humans

2. Gene therapy.

This is a complicated question with a somewhat complicated answer. The quick and simple answer is that we don't know how much time we'll need to do this, or if we can do this.

Changing genetic codes in humans is not a simple procedure because the human body is complex. One of the complexities is that genes themselves are not the only things that would need to be changed to cure/prevent certain diseases. Genes are kind of like blueprints for buildings or patterns for sewing - there are entire processes between them and the "end result", whether the end result be a trait like brown eyes or a medical issue like cancer. In these processes are regulation of the genes themselves and the interactions of the gene products (which are very often proteins) with other molecules in the body, so curing/preventing diseases is not as simple as changing the genes themselves.

For example, we have found that some genes linked to cancer are essential to the normal functioning of bodies! If we were to really try to develop gene therapy as a viable option for disease prevention/treatment, we would need to extensively study how the manipulation of different genes affects the human body, without undesirable side effects. These kinds of experiments would take many decades and many brave volunteers, so we do not have an estimate of how long the development process will take before gene therapy becomes practical, if it does become practical.

It is hard to know this for sure, but it may never happen.

Ordinarily, it is not possible to alter the genetic code of an already living being such as a person. You can alter their sperm and eggs and this what children they will have in the future, but once a person is even a fetus, let alone born, it's too late. The reason why this is the case is because you would have to alter the DNA of every cell in a person's body, not just a single cell like a sperm or egg.

There is one possible exception to this, however: viruses. Viruses implant themselves into the DNA of living things that they infect, which means that if you want to implant someone with a gene that would undo a disease, then a virus could do that. You would just have to come up with a virus that isn't otherwise harmful (despite the bad reputation that viruses have, there are many viruses that do not cause disease themselves). The ability to give people non-harmful viruses that would transfer genes could start almost at any time now, but it could also be many decades yet. It is hard to predict such inventions!