Ansa Biotechnologies Announces Successful de novo Synthesis of World’s Longest Oligonucleotide at 1005 Bases

EMERYVILLE, Calif.--(BUSINESS WIRE)-- Ansa Biotechnologies, Inc., a pioneer of next-generation DNA synthesis, today announced the successful de novo synthesis of the world’s longest DNA oligonucleotide ever reported to be produced in a single synthesis.

The 1005 base sequence encodes a key part of an AAV vector used for gene therapy development and contains complex features, including strong secondary structures and high GC content, which are extremely challenging to synthesize using conventional methods that require assembly of shorter oligonucleotides. The “Ansamer™” oligonucleotide was cloned using standard molecular biology techniques and found to contain approximately 28% sequence-perfect molecules, indicating an industry-leading average stepwise yield of approximately 99.9% during its synthesis.

Since the advent of the first method for chemical oligonucleotide synthesis over 60 years ago, improvements in the length and quality of oligonucleotides that can be synthesized have unlocked new applications that transformed our relationship with the natural world. The ability to synthesize 20-30 base molecules enabled the development of PCR and DNA sequencing, which laid the foundations of recombinant DNA technology and molecular diagnostics. Synthesis of 50-100 base molecules enabled new techniques for precise manipulation of DNA, including site-directed mutagenesis and genetic engineering. Today, high-throughput synthesis of oligonucleotides up to 350 bases enables genome-wide CRISPR experiments and new methods for 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 that it can produce due to intrinsic limitations.

The next frontier in oligonucleotide synthesis is the direct synthesis of gene-length sequences. “Synthesis of a 1005mer represents a major milestone for the field and is beyond what many thought was possible,” said Daniel Lin-Arlow, Ph.D., CEO and co-founder of Ansa Biotechnologies. “Our extremely long Ansamer oligonucleotides will enable us to manufacture genetic constructs for researchers much faster, more reliably, and with fewer sequence limitations than what is currently possible.”

There is increasing demand from scientists for gene-length synthetic DNA for applications such as cell and gene therapies, protein engineering, biomanufacturing, and for fundamental life sciences research. Longer sequences are currently made by “stitching together” shorter oligonucleotides, but the process struggles with sequences that contain certain features such as secondary structures, repeats, and high or low GC content. However, these features are often essential to the function of the DNA. Ansa’s approach overcomes the challenges associated with assembling these types of sequences from shorter oligonucleotides by instead directly synthesizing them as a single, ultra-long oligonucleotide.

Ansa’s proprietary enzymatic oligonucleotide synthesis technology is based on its patented Polymerase-nucleotide Conjugate reagents that can rapidly extend a DNA molecule by one base at a time. The conjugates, which comprise a template-independent polymerase tethered to a single nucleotide via a linker, offer significant advantages in terms of speed and flexibility over other enzymatic synthesis approaches based on free nucleotides. Additionally, Ansa is developing a series of highly multiplexed, custom instruments and informatics tailored for specific production capabilities and downstream applications.

“We’ve made rapid progress in the evolution of our technology platform, but this is just the beginning,” said Sebastian Palluk, CTO and co-founder of Ansa Biotechnologies. “Our technology has the potential to revolutionize life sciences research and biological engineering.”

Ansa will be initiating an Early Access Program for clonal synthetic genes in April 2023. Access to Ansa’s highly complex clonal DNA will empower scientists to explore areas they have not been able to previously because the sequences were too difficult to synthesize.

To join the Early Access Program or learn more about Ansa Biotechnologies, please visit ansabio.com/signup.

About Ansa Biotechnologies

Ansa Biotechnologies is building a fast and reliable DNA synthesis service to accelerate synthetic biology research. Our core technology is a novel DNA synthesis method based on enzymes that is faster, cleaner, and more accurate than existing methods. The company is headquartered in Emeryville, CA. For more information, visit ansabio.com or follow on Twitter and LinkedIn.

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