February 24, 2024

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1005 bases: An enzymatic DNA synthesis company sets a record

1005 bases: An enzymatic DNA synthesis company sets a record for the length of de novo DNA synthesis



 

1005 bases: An enzymatic DNA synthesis company sets a record for the length of de novo DNA synthesis.

Recently, Ansa Biotechnologies , a pioneer in next-generation enzymatic DNA synthesis , announced that it successfully synthesized 1005 bases of DNA from scratch , which is currently the longest DNA oligonucleotide synthesized in the world, and has industry-leading synthesis accuracy.

 

1005 bases: An enzymatic DNA synthesis company sets a record for the length of de novo DNA synthesis

 

It is reported that the 1005-base DNA sequence contains the key part of the adeno-associated virus (AAV) vector for gene therapy, and has a complex secondary structure and high GC content.

Synthetic approaches The way short nucleotides are synthesized for reassembly is extremely challenging.

Among the sequences synthesized this time, 28% of the sequences are completely correct, which shows that during the synthesis process, the average yield per step is about 99.9%, which is at the leading level in the industry.

 

Since the first chemical synthesis of oligonucleotides was developed more than 60 years ago, improvements in the length and quality of oligonucleotides that can be synthesized have opened up new applications and transformed our relationship with the natural world.

 

The ability to synthesize 20-30 bases in length enabled the development of PCR and DNA sequencing, laying the foundation for recombinant DNA technology and molecular diagnostics.

The ability to synthesize 50-100 bases in length has enabled new techniques for the precise manipulation of DNA, including site-directed mutagenesis and genetic engineering.

 

Today, high-throughput synthesis of oligonucleotides up to 350 bases in length enables genome-wide CRISPR experiments and new approaches to protein engineering.

However, the current gold standard for oligonucleotide synthesis, the nucleoside phosphoramidite method, has reached a plateau in the length and quality of oligonucleotides it can produce due to its inherent limitations .

 

The next frontier in oligonucleotide synthesis is the direct synthesis of gene-length sequences .

Dr. Daniel Lin-Arlow , CEO and co-founder of Ansa , said the synthesis of 1,005 bases of DNA was a major milestone in the field, beyond the imagination of many .

Ansa’s ultra-long “Ansamer™” oligonucleotide synthesis platform will allow us to make genetic constructs for researchers faster, more reliably, and with fewer sequence constraints than is currently possible.

 

Currently, scientists are increasingly demanding gene-length synthetic DNA for use in cell and gene therapy, protein engineering, biomanufacturing, and basic life science research.

Longer DNA sequences are currently fabricated by “splicing” shorter oligonucleotides, but the process faces many sequence-specific challenges, such as DNA secondary structure, repetitive sequences, and high or low GC content.

Ansa’s enzymatic synthesis method overcomes the challenge of assembling these specialized sequences from shorter oligonucleotides, instead directly synthesizing them as a single ultralong oligonucleotide .

 

Ansa’s enzymatic oligonucleotide synthesis technology is based on its patented polymerase nucleotide conjugation reagents that rapidly extend DNA molecules one base at a time.

These conjugates consist of a template-independent polymerase attached to a single nucleotide via a linker, offering significant advantages in speed and flexibility over other free nucleotide-based enzymatic syntheses.

 

The technology was published in the journal Nature Biotechnology in June 2018 , the title of the paper is: De novo DNA synthesis using polymerase-nucleotide conjugates .

 

The main authors of the paper, Daniel Lin-Arlow and Sebastian Palluk , founded Ansa Biotechnologies in 2018, and the company has currently completed more than $80 million in seed and A rounds of financing.

 

1005 bases: An enzymatic DNA synthesis company sets a record for the length of de novo DNA synthesis

 

 

Ansa co-founder and chief technology officer Sebastian Palluk said that Ansa has made rapid progress in the development of technology platforms, and this is just the beginning.

This technology has the potential to revolutionize life science research and bioengineering.

 

It is reported that Ansa will launch an early access program for cloning synthetic genes in April 2023.

Obtaining Ansa’s highly complex cloned DNA will allow scientists to explore areas that were previously inaccessible because the sequences were too difficult to synthesize.

 

 

 

 

 

 

References :
https://www.nature.com/articles/nbt.4173

1005 bases: An enzymatic DNA synthesis company sets a record for the length of de novo DNA synthesis

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