"De novo" means "starting from scratch", that is: you type the desired sequence into a computer, and the synthesize it.
The "de novo" part is important, because it distinguishes this from the already well solved problem of duplicating DNA from an existing DNA template, which is what all our cells do daily, and which can already be done very efficiently in vitro with polymerase chain reaction.
Many startup companies are attempting to create more efficient de novo synthesis methods:
Notably, the dream of most of those companies is to have a machine that sits on a lab bench, which synthesises whatever you want.
TODO current de novo synthesis costs/time to delivery after ordering a custom sequence.
The initial main applications are likely going to be:but the real pipe dream is building and bootstraping entire artificial chromosomes
- polymerase chain reaction primers (determine which region will be amplified
- creating a custom sequence to be inserted in a plasmid, i.e. artificial gene synthesis
News coverage:
- 2023-03 twitter.com/sethbannon/status/1633848116154880001
AnsaBio created the world's longest DNA oligo produced using de novo synthesis! 1,005 bases! 99.9% stepwise yield
- 2020-10-05 www.nature.com/articles/s41587-020-0695-9 "Enzymatic DNA synthesis enters new phase"
Nuclera eDNA enzymatic de novo DNA synthesis explanatory animation (2021)
Source. The video shows nicely how Nuclera's enzymatic DNA synthesis works:- they provide blocked nucleotides of a single type
- add them with the enzyme. They use a werid DNA polymerase called terminal deoxynucleotidyl transferase that adds a base at a time to a single stranded DNA strand rather than copying from a template
- wash everything
- do deblocking reaction
- and then repeat until done
The third one from Cambridge after:
Using de novo DNA synthesis to synthesize a genes to later insert somewhere.
Note that this is a specific application of de novo DNA synthesis, e.g. polymerase chain reaction primers is another major application that does not imply creating genes.
Using de novo DNA synthesis to synthesize entire Chromosomes.
Synthesizing the DNA itself is not the only problem however.
You then have to get that DNA into a working living form state so that normal cell processes can continue:
- for viri see: synthetic virus
- for bacteria, you have to inject it into a cell
- for placental animals, you also have to somehow simulate a compatible placenta. It is likely easier for eggs.
Multicellular questions:
Apparently achieved for the first time in 2021: www.jcvi.org/research/first-self-replicating-synthetic-bacterial-cell by the J. Craig Venter Institute.
Basically a synonym for doing a large chunk of de novo DNA synthesis.
Man-made virus!
TODO: if we had cheap de novo DNA synthesis, how hard would it be to bootstrap a virus culture from that? github.com/cirosantilli/cirosantilli.github.io/issues/60
Is it easy to transfect a cell with the synthesized DNA, and get it to generate full infectious viral particles?
If so, then de novo DNA synthesis would be very similar to 3D printed guns: en.wikipedia.org/wiki/3D_printed_firearms.
It might already be possible to order dissimulated sequences online:
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