June 10, 2016 at 12:52AM

Today I Learned: 1) There's a new player in the genome editing game called NgAgo (short for Natronobacterium gregoryi Argonaute). Argonaute proteins important components of the RNA interference system in eukaryotes, which destroys RNAs that match any double-stranded RNA found in the cell, probably evolved first to combat RNA viruses*. Argonautes are the nucleases that do the RNA cleaving when RNA interference is invoked. They can also be used to cut DNA under specific circumstances, and they've been used in CRISPR/Cas-like ways in bacteria, but until now argonautes haven't been used in eukaryotes because they only function at high temperatures. Enter NgAgo. The argonaute found in the bacteria Natronobacterium gregoryi was discovered by searching for proteins with homology to other bacterial argonautes, and happens to work at body temperature. That makes it an attractive alternative to Cas9 as a programmable DNA cutter. There are a few differences between the two enzymes, which make NgAgo more attractive at least for some applications. One inarguable advantage of NgAgo is its lack of PAM sequence -- it can be targeted to any DNA sequence, not just DNA sequences next to a PAM. One arguable disadvantage is NgAgo's mechanism of cutting -- instead of making a clean cut, NgAgo tends to cut each strand *back* a few nucleotides, causing deletions. That could be good, if all you want to do is knock out a gene, or totally irrelevant if you're going for some kind of template-mediated recombination, but for certain kinds of precision edits, it's pretty annoying. One feature that's just plain different is that NgAgo uses a *DNA* guide instead of an RNA one. That means that it's really simple to induce cutting in a petri dish, because you can just drop in a DNA oligo (like, literally drop in, with a pipette) instead of having to transcribe out delicate RNA or put together some sort of guide expression construct. It also means you can't easily turn on NgAgo with some sort of genetic circuitry, because it's hard to make a cell produce DNA oligos. The authors who just published about NgAgo also claim that NgAgo is less prone to off-target cutting than Cas9... I'm inclined to chalk that up to NgAgo being new and relatively unvetted, and I give it about 25% odds that NgAgo is actually significantly more accurate than Cas9. *or, stated somewhat less teleologically, evolved because pre-RNA interference eukaryotes were more vulnerable to RNA viruses. 2) ...how to ship scientific materials internationally! There is, as you might imagine, some paperwork. There was more such paperwork than I expected, but not as much as I probably should have. I also learned a bit about European address formats. I didn't know that most European countries use a postal code equivalent to a US ZIP code. Also, a number of countries, including Switzerland and Denmark, use a state-equivalent code in addition to the ZIP. Others have an optional *country* code. Perhaps unsurprisingly, postal codes from Great Brittain are the longest and have the most complex address format of any European country I've seen... or, indeed, of any country I've seen at all.... 3) There's a short film with a screenplay written by an AI. It's called Sunspring, and it's... pretty typical neural net output. Check it out here, it's probably worth the 10 minutes: http://ift.tt/1UFIfij