Gene editing is changing the world!

Imagine if I told you, you have the ability to cure a loved one who is suffering from a fatal disorder. Well guess what you can! Thanks to the latest advances in gene editing, we now have the opportunity to change our DNA to protect ourselves from some harmful diseases and potentially alter some parts of our physical appearances.

Gene editing

Gene editing (also known as genome editing) is a group of technologies that enable scientists to change an organism’s DNA. This emerging technology allows genetic material to be removed, added or replaced in specific locations within the genome. Over the years several approaches have been developed, the most recent being CRISPR-Cas9. This system is more exciting for scientists as it is faster, cheaper, more accurate and more efficient to use than the existing methods. Currently there is a lot of research being conducted to understand and expand the use of gene editing to help prevent and treat major human diseases such as cancer, heart disease, mental illness and HIV.

How it works

Earlier, scientists were mainly focused on editing the genomes of bacteria and other organisms. This study helped make the discovery on how genomes are connected to physical traits such as eye colour and disease. Over the years scientists have discovered four different methods to edit genes:

Homologous recombination

The earliest method that was used by scientists to edit genomes in living cells was called homologous recombination. This method was basically the exchange (recombination) of genetic information between two similar (homologous) strands of DNA. Scientists began using this technique in the late 1970s to make observations on yeast and other organisms. To perform homologous recombination in a lab, one person needs to isolate DNA fragment sequences that are similar to the portion of the genome that is about to be edited. The isolated fragments can be directly injected into individual cells or can be taken up by cells using special chemicals. Once it is inside of a cell, the DNA fragments can recombine with the cell’s DNA and replace the specific portion of the genome. The use of this method has now been limited due to the fact that it is quite inefficient for most cell types and the probability of success is very low.

Zinc-finger nucleases (ZFN)

In the 1990s researchers started using ZFN to improve the specificity of genome editing and reduce the off-target edits. The structures of this method were designed from natural-occurring proteins that were discovered in eukaryotic organisms. Experts in this area can build these proteins to hold onto specific DNA sequences in the genome and cut the DNA. Once they are bonded to the DNA sequence, the ZFNs cut the genome at the specific location which allows scientists to either delete the target DNA or replace it with a new DNA sequence. Although ZFNs helped improve the success rate of editing genome by 10% and was highly more efficient then homologous recombination, it is still difficult and time-consuming to design and construct.

Transcription activator-like effector nucleases (TALENs)

In 2009, TALENs began to be used as another method for editing genes. Just like ZFNs, TALENs are made from proteins found in nature and are capable of holding onto specific DNA sequences. While TALENs and ZFNs are quite comparable in how they can create edits to the genes, TALENs beat ZFNs in efficiency and simplicity.

Clustered regularly interspaced short palindromic repeats (CRISPR)

Even though ZFN and TALEN technology increase the specificity and efficiency of gene editing, both methods are pretty expensive and complicated to use in a lab. This is why CRISPR is a game changer. It is more simple to use with a lot less assembly required. CRISPR’s relation to DNA sequences was first discovered in the 1990s but it wasn’t till the 2000s when the scientific community understood its ability to recognize specific genome sequences and cut them using Cas9 protein (a protein that has DNA cutting abilities). CRISPR is used by bacteria as an immune system to kill viruses and now it has been adapted for use in the lab.

With CRISPR:

• Strands of RNA and DNA can secure each other if they have matching sequences.
• The RNA part of CRISPR directs enzymes to the targeted DNA sequence.
• Cas9 cuts the genome at this location to make an edit.
• CRISPR can then delete or insert new DNA in the genomes.

According to a study conducted by a group of scientists, CRISPR was found to be 6x more efficient than ZFNs and TALENs.

Uses of gene editing

Basic research on gene editing has helped scientists understand basic biology and underlying diseases, as well as discovering new therapeutic targets. Researchers rely on gene editing tools to find the connection between genotype (genes) and phenotype (traits). A common experiment that happens is usually to model human disease in mice by either deleting or editing a certain gene that might contribute to the disease. This helps researchers determine whether they need to make specific changes to the genome. Many diseases like cancer and asthma have genetic bases. Through this application of genome editing technologies, physicians might eventually be able to advise specific gene therapy to make corrections and prevent, reverse or stop the spread of disease.

There are two different types of gene therapies

Germline therapy: Germline therapies can change genes in reproductive cells. These changes can be passed down from generation to generation. Eventually, germline therapies can potentially prevent inheritance disease.

Somatic therapy: Somatic therapies, on the other hand, target non-reproductive cells. The changes that are made in these cells only affect the person that receives the gene therapy and it does not pass to any future generations. These can be used to slow or reverse disease.

In relation to the two types of therapies, somatic therapy is less controversial and therapies using this approach are usually under development in research and commercial labs all over the world. Treatment for HIV and cancer are currently being tested in clinical trials in patients. Germline therapies have a greater number of ethical hurdles because of their ability to affect future generations. Critics have called attention to the high possibility of germline therapies paving its way for genetic enhancement. Although all this sounds super cool, there is still an unknown risk for off-target edits or unintended edits. Another challenge for gene therapy is that there is still a lot to learn about which genes are involved with what disease and how different genes can 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 still working on learning more about genetic changes and environmental influences that combine to result in disease and how genes interact with one another. Adding on to that point, scientists need to learn more about how genes are controlled and how variants in these controlling regions of the genome are related to the disease risk.

Advances in gene editing

The history of genome editing technologies shows a remarkable progress in this field and also relays the critical role that basic science research plays in the development of research tools and potential disease treatments.Some important events from over the years include the discovery of the double helix, recombination DNA, human cancer therapies, the invention of CRISPR, and so much more.

Gene editing and medicine

Ever since scientists learned that different changes in DNA can cause cancer, they have been researching ways to correct those changes by manipulating DNA. Over the years, several methods of gene editing have been developed but neither of them fit into the cheap, easy and quick category.

However, 2013 was a game changer and CRISPR was introduced. As soon as researchers understood how CRISPR worked it became a mainstream methodology used in so many cancer biology studies. Now CRISPR is actually doing in-person trials for people with cancer. As of 2019, medical applications of CRISPR-cas 9 are working quite well. The first ever results trickled in from trials in people and more trials are being launched. In the years to come, researchers are looking ahead to more sophisticated applications of CRISPR.

Gene editing and Alzheimers

We’ve all heard of Alzheimer’s — it is probably one of the most brutal disorders from many different perspectives. This disorder typically affects aging brains and starts to eat up their ability to think and makes it harder for them to hold onto their memories. Alzheimer's is growing at a shocking rate and there is no treatment or cure! The thing is no one really knows what exactly causes this disease. There are so many theories but not many biological characteristics that are found in every person with this disease.

David Liu (one of the best scientists specialized in gene editing) has come up with a theory. The idea is to create a treatment that would flip the baseline letters of the DNA strand — G, A, T and C — and turn it into APOE4 or another type of gene known as APOE3 into APOE2. A couple years ago there was strong science linking APOE2 to Alzheimer’s disease and promising signs that base editing could tweak that gene. Other researchers also showed that people with a similar gene, APOE2, are between 66% and 99.6% less likely to develop Alzheimer’s disease. One of the first tests of this science is to see if it can be used to install a gene called APOE2 that is believed to significantly reduce the risk of a person getting Alzheimer’s.

So how is this going to work? Using CRISPR, scientists can insert genes related to Alzheimer’s, or its protection, into an iPSC — either from a healthy donor, or someone with a high risk of dementia, and observe what happens. A brain cell is like a humming metropolitan area, with proteins and other molecules circling around. Adding in a dose of pro-Alzheimer’s genes, for example, could block up traffic with gunk, leading scientists to figure out how those genes fit into the larger Alzheimer’s picture. So let’s put it in another way, for those of you who love watching movies like me, it’s like adding into a cell, a gene for Godzilla and another for King Kong. You know both could mess things up, but only by watching what happens in a cell, you’ll know for sure. Liu’s work focuses on a gene that is known to people up to 99.6% less likely to get Alzheimer’s.

All this sounds so exciting and I can’t wait to see how gene editing can change the future of disease and help us lead longer and more fulfilling lives.