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Findings in title quoted from the linked summary by Manuel Ansede, 16 Jan. 2023, EL PAÍS.

Excerpt:

>The gene editing techniques that have revolutionized medicine since 2016 could also be used to treat common heart diseases, the number one cause of death in humans, according to a study published recently by one of the world’s leading scientists, Eric Olson, from the US.

>His team was able to modify two letters – or bases – of the approximately 3 billion that make up the DNA of a mouse. This change was enough to silence a protein linked to multiple cardiovascular problems.

>Olson is cautious, but highlights the potential advantages of this new strategy: since heart cells last a lifetime, it is only a matter of making the change once.

>Olson, from the University of Texas Southwestern Medical Center, talked about his research to EL PAÍS via videoconference from Dallas, Texas, accompanied by a Spanish colleague from his laboratory, biologist Xurde Menéndez Caravia, co-author of the new study, who explained that the results of the first proof of concept are very promising.

> 

>The technique appears to be safe in mice; now, what comes next is to explore the possible long-term effects.

>The researchers modified the recipe for a protein called CaMKII delta, whose hyperactivation causes various cardiovascular problems such as arrhythmias, heart failure or damage to the heart muscle after a myocardial infarction.

>By changing two letters in the recipe, the resulting protein is not hyperactivated. Olson’s team used this technique in mice with cardiac damage after a heart attack, a phenomenon known as ischemia-reperfusion injury. The organs of the rodents recovered their function after the genetic editing of their cells.

>“As a therapy aimed at large population groups, it would be a revolution. We are talking about myocardial infarctions: potentially millions of people could be treated with this technique,” says Menéndez Caravia.

Lebek S., et al. Ablation of CaMKIIδ oxidation by CRISPR-Cas9 base editing as a therapy for cardiac disease. Science (2023). https://doi.org/10.1126/science.ade1105

so how does the edit actually happen? like how do you edit the DNA of all the heart cells (or enough of them) to fix this?

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If it’s like other forms, typically through a viral vector. The carrier molecule drops a specific piece of DNA to a gene and overwrite/replacing it with a correct copy.

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Is that Jim Carry from 2078? Sorry mods

Bruce Almighty. For only he is wise enough to find this out.

“the technique is still not perfect and can produce some unwanted letter changes; this occurred in Eric Olson’s mice, although apparently without adverse effects.”

I am optimistic these off-target effects can continue to be lowered. Their existence will be a major hurdle going forward.

I’m too lazy to look it up, is this applied intravenously and changes all cells it encounters, or just injected directly into the target tissue?

Well, alrighty then.

“Two letters”

It’s two amino acids.

Probbaly targeting mesenchymal stem cells, the pluripotent precursor to cardiovacular cells.

As other have mentioned, virally at the target location (heart cells last a lifetime). But also, you don't need to replace all the DNA. Just a decent majority to quell the expression of those genes.

Simple answer. It can be made to target specific cell types. But like in nature, there is probability distribution, a small chance for errors is always present.

But again, if the change happens in the wrong cell type, it can perhaps be neglected, because the changed gene sequence is not "used" in this type of cell.

Life is a very complex systems, wich is ultimately build on the sequence of just four molecules. This sequence is the "memory" (in the therm of computer science) of life. Like we use 0/1 for digital memory of informations.

I find it fascinating. Wish you well.

Two letters were converted which leads to 2 amino acids being changed. So you are right, but quite unnecessary to point it out.

Methionine281 (ATG) and M282 were mutated to Valines (GTG) so only 2 A to G conversions.

from the article: >We packaged the ABE components in adeno-associated virus serotype-9 (AAV9) using a split-intein trans-splicing system to accommodate the large size of ABE8e and sgRNA6. AAV9 was chosen as the delivery system because it effectively infects the hearts of mice and large mammals (2, 4). To ensure cardiac specificity, we used the cardiac troponin T (cTnT) promoter to drive ABE8e expression.

Referring to them as “letters” is a part of the oversimplification that is so rife in academia right now. I am involved in the pipeline for new nurses, and I wouldn’t want 90% of these kids having any involvement in my own health care.

This ''oversimplification'' is definitely not a problem here. It's journalism, it's supposed to be more simplified and even in the article they mention in the first paragraph that it's base modification that they are reffering to with that AND they examplain in tl;dr how it works (so that you know what level science journalism is done on). They could write out that they mean ''letters of the genetic code'' but contextually everyone generally familiar with it should be aware that that's alluded too.

And honestly if you want to be so overprecise on the genetics then saying that they exchanged two amino acids instead of two ''letters/nucleotides'' is practically more ''wrong'' because the difference in aa sequence is a downstream effect of nucleotide conversion and not how mutagenesis principally works.