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Basic Genomics Bets on RNA-seq Market With Synthetic Long-Read Technology

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NEW YORK – Swedish startup Basic Genomics is eyeing the RNA sequencing market with a new synthetic long-read technology that it promises to be accurate, accessible, and cost-effective.

The Karolinska Institute spinout closed an SEK 11.7 million ($1.2 million) investment round last week to support the development of its so-called BaseCode technology, which it hopes to bring to the market in the upcoming years, though it did not provide a specific timeline.

"The average human transcript is [around] 1.4 kb or 1.5 kb — they are relatively small contigs, and they are perfect for a synthetic long-read technology," said Basic Genomics Cofounder and CEO Gert-Jan Hendriks.

Hendriks helped develop the technology underpinning BaseCode during his time as a postdoctoral researcher in Rickard Sandberg's lab at the Karolinska Institute. A single-cell biologist, Sandberg is also a cofounder of Basic Genomics and currently serves as its CSO.

BaseCode is a "combined chemistry and software" product for RNA sequencing and analysis, Hendriks said. More specifically, the technology performs "error prone" reverse transcription on RNA samples, generating "specific errors, but randomly throughout every cDNA molecule," he said.

Hendriks declined to disclose further details of how BaseCode induces errors, other than noting that it incorporates a promiscuous base during cDNA synthesis. "There is a very high rate of errors, but they are random," he noted. "Because they are randomly located, they become an identifying barcode" for each molecule.

After the error-inducing reverse transcription, the cDNAs undergo regular RNA-seq library prep and short-read sequencing, Hendriks said. The sequencing reads are then informatically stitched together, using each molecule's error profile, to produce synthetic long reads.

Depending on the quality of the RNA molecules, Hendriks said, BaseCode can produce synthetic long reads that exceed 1 kb. The input requirement is between 2 ng to 6 ng of RNA, and the turnaround time for the sample prep workflow — from RNA to sequencing-ready libraries — is about 12 hours.

While BaseCode is compatible with any short-read technology in principle, Hendriks said, the product will initially be optimized for Illumina sequencing.

Benchmarking data for the BaseCode method is not yet available, he said, and the company has yet to decide on a kit format and pricing.

Once the product is launched, BaseCode's target customers will be researchers who want to study full-length RNA transcripts, including those focusing on isoform analysis, Hendriks said. This would put the company in competition with long-read sequencing technologies, which have been touted for full-length RNA analysis, as well. While it remains to be seen how BaseCode stacks up against long-read sequencing, Hendriks said that "the benefit of short-read sequencing is that you carry super-high base accuracy into everything you do."

With the money raised, Hendriks said the company plans to continue developing and commercializing the BaseCode technology, expanding operational activities, and building up a commercial team.

Based in Stockholm, Basic Genomics currently has four full-time employees, a number it plans to increase, though Hendriks declined to provide specifics.

Currently, Basic Genomics also offers BaseCode as a service to select customers who want to test out the technology. A formal early-access program will be next, Hendriks said, but "it is too early to really say much about [it]."