The entire lake had just been treated with herbicides and everyone was supposed to stay out of the water for at least 24 hours. Last summer I was at a marina and recalled a conversation I had with a boat mechanic. If/when increased cancer from CRISPR-Cas9? I won't go further down this rabbit hole but I give you that taste, to show you the underlying double-strand break approach of CRISPR-Cas9 has follow-on effects which are not good. Telomeres are highly sensitive to oxidative DNA damage and other forms. Cellular senescence is triggered by P53 (and similar P16 and P21) as well as telomeres being too short. There are other facets to aging but you can always link them back to genetic damage/modification.įor example, P53 activity goes into overdrive to repair double-strand breaks. The shorter they get, the less likely they are to protect what's sandwiched between. Telomeres - Like the plastic caps on your shoelace, these protect the ends of your chromosomes.P53 - Known as the 'tumor suppressor' protein, it goes to work against damaged DNA, particularly double-strand breaks.Cellular senescence - Discovery that human cells can only replicate less than 70 generations in culture.While that specific theory has been largely disregarded due to lack of evidence, variations followed such as Leo Szilard's two-hit model of somatic mutation accumulation which made more sense, but did not and could not incorporate future findings such as: Eventually reaching a catastrophic level which is incompatible with cellular survival. Specifically, it results from a breakdown in the accuracy of protein synthesis within somatic cells. Summarized, aging equals the accumulation of genetic errors. What causes aging? The error catastrophe theory of aging was originally proposed by Leslie Orgel in 1963. Fortunately, the only ones which cause cancer are those mutations which cause uncontrolled cell replication AND don't get taken out by your body's defenses in time.Īs far as the rest of mutations? We don't really know what they do, but we do know they're not good. You have an estimated 37 trillion cells in your body and on any given day, trillions of mutations occur. We didn't have the technology to do the rest until last year. The 'complete' mapping widely publicized nearly 20 years ago was actually 92%.

Heck, we didn't even fully map the human genome until 2022. With 3 billion letters in the human genome, we don't know what the vast, vast majority of mutations do. Not all mutations cause cancer, but ALL cancers are the result of a mutation.

They are completely intentional! That is how the editing is done - breaking both strands of the DNA in order to modify them. Those deletions, translocations, and fusions in the DNA are permanent mutations once they occur.ĭSBs are not a side effect of CRISPR-Cas9. With DSBs, genomic rearrangements are much more likely to occur. That attached side acts as a guide, meaning the repair mechanisms have more to go off of, clues as to what is missing on the broken side. Why? Because the genetic blueprint is completely broken, making accurate repair difficult.Įven with single-strand breaks (SSBs) there is still the other side attached. Known as double-strand breaks (DSBs), these are the absolute worst type of damage. See that one in the middle with the radiation symbol? That's the same type of damage you are doing with CRISPR-Cas9. Komor Lab, University of California San Diego I could write a book about this subject but to keep it short and sweet, this graphic will help you understand: The vast majority of damage comes from oxidative stress and normal cellular chemical reactions, such as depurination and depyrimidinations. It is true our cells are well-equipped at repairing DNA damage, but not all types.

So is it really that big of a deal if you damage them some more with CRISPR-Cas9 editing? The big problem with CRISPR-Cas9 or 'CRISPR 1.0'ĭue to environmental factors and normal metabolic processes in the cell, it has been estimated that each cell in your body experiences 10,000 to 1,000,000 molecular lesions (damages) per day.

In the short term, CRSP may be the better investment, despite the potential cancer-causing side effect of its editing, a side effect PRME avoids altogether. Despite being founded 10 years ago, CRISPR Therapeutics ( NASDAQ: CRSP) could very well lose out to 3-year-old Prime Medicine ( NASDAQ: PRME). Sometimes it's the tortoise and not the hare which wins the race.

Horizon therapeutics crispr