CRISPR-cas9 is one of the most promising new developments in medicine, and in science in general.
For decades, editing genes was a laborious, difficult and expensive process. It could take many months to years to change just one gene, and it would cost hundreds of thousands of dollars, while requiring a state of the art lab. Presently, with CRISPR-cas9 you can change a gene in less than a day at a cost of around 50 dollars.
However, CRISPR-cas9, how revolutionary it may be, is being superseded by even better versions.
In other words, CRISPR 2.0 has arrived.
This is technology like CRISPR-cpf1, which is a smaller, less complex version of the original CRISPR-cas9 protein. Because of its smaller size, CRISPR-cpf1 is easier to insert into viruses, which can carry it into cells. Another advantage is that CRISPR-cpf1 cuts the DNA in a better way (it creates "sticky ends" instead of "blunt ends").
Another example is DNA base editors. The team of professor David Liu at Harvard University developed an adenine base editor (ABE), which is a hybrid of a cas9 protein and a protein that can edit specific pieces of DNA, called adenines.
Base editors are much more accurate than CRISPR-cas9, and this by a long margin. Contrary to CRISPR-cas9, they create much less double-strand breaks and other (off-target) mutations.
The adenine base editor can change an adenine base into a guanine base, which could fix about half of the 32 000 point mutations that cause disease (point mutations account for about two third of the mutations in the human genome associated with disease - about 32000 out of the 50000 disease-causing mutations).
Besides CRISPR-cas9, also CRISPR-cas13 has been developed, which can modify RNA instead of DNA, opening up a whole new world of possibilities to modify the transcriptome, enabling more fine-tuned control of cells compared to editing the genome (DNA).
The toolbox to manipulate the genome, transcriptome, and epigenome is being extended on a continuous basis, paving the way for the manipulation of cells, and life, in ways never seen before.
Many genes involved in the aging process have been discovered. These genes can in part predict our life span and our risk of aging-related diseases.
A well-known gene is the APOE gene. This gene is the most important predictor of the risk of contracting Alzheimer’s disease.
The APOE gene comes in 3 variants: APOEe2, APOEe3 and APOEe4. You always carry 2 variants. The e4 variant confers an increased risk of Alzheimer’s disease. People who carry one e4 variant (for example APOEe4/APOEe3), have twice the risk of developing Alzheimer’s disease. People who carry both e4 variants (APOEe4/APOEe4) have a nine times increased risk of Alzheimer’s disease.
Of course, nine times a small risk still equals a small risk, especially when you are still young (‘young’ referring to 50 to 70 years). However, research shows that e4 carriers have life expectancies that are 6 years shorter on average.
Interestingly, it seems that people who carry the e4 variant(s) have strong immune systems. They can ward off infections better. This would have been a big advantage in prehistoric times, when infectious diseases were rampant.
However, in this day and age, with improved hygiene and increased survival rates into older age, the tables are somewhat turned, and the e4 variant seems to be a disadvantage because the strong immune response can accelerate the aging process and increase your risk of Alzheimer’s disease.
The APOE gene is also involved in cholesterol and fat metabolism, and e4 carriers tend to accumulate more fat and cholesterol in their blood, raising the risk of cardiovascular disease, another aging-related disease.
About 65% of people of European ethnicity carry the e3 variant, and 25% the e4 variant.
Author: Kris Verburgh, MD