Chemical modifications of DNA are so amazing, and underpin so much DNA related research and engineering. Illumina and Moderna would not exist without DNA mods. It’s very cool that the set of tools is expanding further!

“ Guided by the removable DNA page numbers, Sidewinder achieves an incredibly high fidelity in DNA construction with a measured misconnection rate of just one in one million, a four to five magnitude improvement over all prior techniques whose misconnection rates range from 1-in-10 to 1-in-30.”

I wonder if this is even a problem, since you could amplify the correct sequence with PCR afterward.

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codesnik 5 hours ago | parent | next [-]

pcr amplifies all sequences, correct or wrong, no? and as I understand it, it works on short snippets the best.

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biophysboy 4 hours ago | parent [-]

It amplifies sequences that contain the two primer sequences on each end of the target. So if you had synthesized sequence XYZ with some mistakes like YZX, then you could target X and Z and purify.

You're correct that PCR has a limited max length, but it is longer and cheaper than vanilla DNA synthesis.

	▲	bookofjoe 2 hours ago \| parent [-]
		Kary B. Mullis Nobel Prize lecture Nobel Lecture, December 8, 1993 The Polymerase Chain Reaction https://www.nobelprize.org/prizes/chemistry/1993/mullis/lect...

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oofbey 3 hours ago | parent | prev [-]

Intuitively I agree some kind of selective amplification should be able to correct for the mistakes. But I think it will be complicated. Because the filtering process needs to be much more complex. It can’t just chemically match to a known subsequence - you won’t know where the mistake might be in a long sequence.

	▲	biophysboy 2 hours ago \| parent [-]
		This is a good point. WXYZ and WYXZ are indistinguishable via PCR. And the possibilities accumulate with more segments.