Um, now, when we talk about in vivo applications where systemic exposure really is a factor, how does the avoidance of double-stranded breaks specifically de-risk your in vivo pipeline compared to, you know, traditional CRISPR-Cas9?

Yeah.

So, um, as I mentioned earlier, base editing is the next-generation editing technology that avoids the double-stranded breaks.

Um, and it results in these consistent gene sequence outcomes, durable correction, um, and, and potentially less genotoxicity than traditional gene editing approaches, right? So I think it's worth actually taking a step back and understanding the mechanism by which traditional CRISPR-Cas9 works.

So the Cas9 enzyme, um, it's a nuclease, and it's directed to a specific location in the genome using a guide RNA.

And that guide RNA then enables the Cas9 enzyme to reach that particular site in the genome, and then cut the DNA by introducing a double-stranded DNA break.

And then what happens is, um, the cells have a surveillance mechanism to sense any damage to the DNA, and so a double-stranded break to the DNA is DNA damage.

Um, talk to us a little bit about how BEAM is engineering delivery vehicles that can bypass the liver to reach, you know, these kind of hard-to-hit tissues without the toxicity seen in, you know, older viral vector models.