[bonsai_spool]

This is not a practical challenge - I order DNA from Twist at these ‘large’ scales trivially without needing to do oligo hybridization magic. The DNA arrives in a month - but considering how many oligos sidewinder calls for, not clear how they could be faster.

[cge]

At a basic level, methods of combining oligos to produce long strands have been known for ages. The challenge is to be able to produce them with low enough error, high enough yield, and enough freedom on sequence. Low error improves your yield, reduces the amount of purification and amplification needed, and lets you make longer strands. Sequence constraints can be significant, too, especially around repeats.

If you're talking about Twist's gene fragment product, they advertise that as maxing out at 5 kb. Most, if not essentially all, of that month delivery time is likely the combination, not the oligo pool production. I think the Sidewinder people are actually using Twist pools; they're doing up to 12.5 kb.

By comparison, we recently needed something in the 20 kb range, with a not-so-great sequence, and it was a multi-month process to have a company produce it.

[amirhirsch]

https://ansabio.com/ advertising 50 kb

[LarsDu88]

How is ANSA bio? I just got hit up by a recruiter for this company at random, and now I see them mentioned on Hackernews

[amirhirsch]

It's a sign! I'm too biased to give you advice.

[LarsDu88]

You work there?

[amirhirsch]

the founder and i lived together at MIT. definitely go work there <3

[kardianos]

Yes. Whole genome sequencing has... some limits. CYP2D6 for instance is an important gene address, yet is rather hard to sequence do to its many copies and minor mutations. If you don't use targeted copy callers, it can be hard to correctly sequence in WGS.

[bonsai_spool]

> Yes. Whole genome sequencing has

We're speaking about gene synthesis, not about DNA sequencing

[dnautics]

> not-so-great sequence

are the limits on not-so-greatness for sidewinder known?

[dnautics]

12kb, you can get three gblocks in a week and change and have them assembled in two days.

[bonsai_spool]

Not sure if the oligo approach would circumvent this concern, but I had a GC-content issue with gene blocks that precluded me from using them. Twist was able to do the synthesis, however (not sure what platform they use for their synthesis and why they were able to offer this).

[sterlind]

out of curiosity, what do you do with them? what's your use case for large DNA?

[bonsai_spool]

For me it makes it easier to study long, alternatively spliced genes.

But there are many use cases - you can see them described on vendors’ pages and even in this new post.