Re: [DIYbio] Purchasing DNA synthesizer

Length, which is a function of reliability

> is it because of business model choices of the companies

Absolutely.

> Some more light on this will be helpful.

I wrote a couple essays on this topic here - https://keonigandall.com/posts/affordable_dna_2.html

> My understanding is synthesis needs to get way more cheaper as per the "data storage" drivers. Wondering if it's just hype or realistically possible.

The reason DNA is expensive right now, IMO, is that companies spend a lot of money on development of technology and the cloning process, and don't have enough users to aggregate the development costs against. You can always just solve the first bit with shittier/older technology, but reduce the requirement of cost aggregation, and therefore get a much more affordable end product.

On Friday, August 19, 2022 at 9:56:24 AM UTC-7 Ravi Ramana wrote:

By Enzymatic synthesis about 5X better you mean in  which factor  - speed or efficiency or length ? 

And oligos being 100x-1000x expensive than what current tech could do - is it because of business model choices of the companies 

or 

you mean the current tech base is amenable for that kinda improvement.  Some more light on this will be helpful. 

My understanding is synthesis needs to get way more cheaper as per the "data storage" drivers. Wondering if it's just hype or realistically possible. 

On Friday, August 19, 2022 at 7:30:21 PM UTC+5:30 Koeng wrote:

Oligos have to be stitched together into genes. Enzymatic synthesis is about 5x, last I heard, better than chemical, but also much more expensive and complicated to run.

> This barrier shd be broken immediately, if so.  

It is very difficult, but not impossible.

On Thursday, August 18, 2022 at 10:17:05 PM UTC-7 Ravi Ramana wrote:

Any specific reasons why the differentials are so high? other than the long writes between gene & oligos?  

Also, you saying currently we could do 0.001 to 0.01 per bp already and its business model choices its' 100-1000X higher presently? That's tall. 

Enzymatic synthesis offerings even don't get those price points as of today. Curious to look at any pointers. This barrier shd be broken immediately, if so.   

On Wednesday, August 10, 2022 at 12:43:36 AM UTC+5:30 Koeng wrote:

@Abizar Yep

@Dan awesome! I'll contact you about that.

@Bryan let's definitely talk!

> making gene-length fragments is pretty standard and inexpensive these days and is offered by a spectrum of commercial groups

Over 200x price difference between genes and oligos. Oligos are about 100-1000x more expensive than they could be with current technology. I am aware of current commercial groups - I used to run the FreeGenes Project and oversaw a few million base pairs of synthesis from Twist.

> The idea of a chip-based oligo assembler has been around for a while but to my knowledge no one has been able to get it to work well

Genscript uses it in production. Already have reached out to Drew Hall + some of the Avery folks, since they're jumping on since the patent is expiring from custom array (just like me)

On Tuesday, August 9, 2022 at 11:52:48 AM UTC-7 Andrew Hessel wrote:

Great that DNA writing is popping up again. It's so foundational yet has received so much less attention than reading DNA. This said, making gene-length fragments is pretty standard and inexpensive these days and is offered by a spectrum of commercial groups. I don't recommend doing it at home/garage/etc if you're planning on working with proteins or short metabolic pathways just because of the economics. Your time and money are better spent on protein/metabolic engineering etc. Also, if you're planning on using older, organic chemistries to make DNA, keep in mind the chemicals required and waste products produced are not great to have around your home or garage. You may want to explore newer enzymatic-based chemistries coming online that are much greener. The idea of a chip-based oligo assembler has been around for a while but to my knowledge no one has been able to get it to work well -- it would be great to have this revisited, but I still would have the oligos pre-synthesized and focus mainly on getting the assembly processes working well. Note that chip-based foundry systems and chip-based test and measurement systems are getting a lot of attention these days. I point people to these two papers to get a sense of where things stand -- Venter's recent review of synbio -- pay particular attention to Figure 4, which describes Avery bio's chip-based DNA synthesis system -- and Roswell's description of their Molecular Electronic chip -- a general purpose, single molecule sensing platform. The problem of making long DNA assemblies necessary for synthetic genomes has not yet been solved. My baseline is E. coli K12 from ATCC, which retails for $400. The genome is about 4.5 megabases. At current synthesis prices, about $0.10 base, K12 would be a $450,000 print job. When it's $450 to print the genome -- and we have base-level control of the entire chromosome -- no one will order the microbe from ATCC again. I look forward to this day.

As Bryan says, onwards and upwards.

Cheers, Andrew

On Tue, Aug 9, 2022 at 5:05 AM Bryan Bishop <kan...@gmail.com> wrote:

Thanks everyone. I am still around (and so is Nathan), and I actually sent an off-list email earlier indicating my interest in funding this project. Onwards and upwards,

- Bryan

https://twitter.com/kanzure

On Tue, Aug 9, 2022, 3:15 AM Brian Degger <brian....@gmail.com> wrote:

https://diyhpl.us/wiki/dna/dna-synthesis.html a the page Bryans on DNA Synth.

Otherwise, search the research papers on microfluidic dna synth. 

Cheers,

Brian

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