Synthego Announces Modified Synthetic sgRNA – Critical for Editing Primary and Stem Cells, and other Challenging Cell Types

Redwood City, California – March 21, 2017 – Synthego, a leading provider of genome engineering solutions, today announces the availability of chemically modified synthetic guide RNA in the CRISPRevolution product family, including modified full length 100-mer synthetic single guide RNA (sgRNA).

Critical for editing challenging cell types such as primary and stem cells, modified guide RNAs provide protection against intracellular immune responses present in primary cells, such as stem cells. Additionally, chemically modified RNA improves in vivo stability by protecting RNA molecules against exonuclease attack – allowing it to persist longer in certain cell types and regions of genomic DNA that can be challenging to edit using conventional guide RNAs.

Synthego’s modified sgRNA are synthesized with 2’-O-methyl analogs and 3’ phosphorothioate internucleotide linkages in the first three nucleotides at both the 5’ and 3’ end of the RNA molecule. It’s currently impossible to make chemical modifications to plasmid or in vitro transcription (IVT) based guide RNAs.

Synthetic sgRNA is chemically synthesized to the highest levels of purity, eliminating the risk of introducing toxins that may be present in IVT-based guide RNAs. In addition, the use of modified synthetic sgRNA also safeguards against the accidental incorporation of DNA into edited stem cells, which can occur as a result of using plasmid or IVT guides.

Matthew Porteus’ research group, part of the Division of Stem Cell Transplantation and Regenerative Medicine at Stanford University Medical School, published breakthrough research in Nature Biotechnology in 2015 demonstrating the use of chemically modified synthetic sgRNA for performing CRISPR genome editing in human stem cells.

"We have found that Synthego provides high quality chemically modified synthetic sgRNA which have become a vital tool for our CRISPR/Cas9 based research program," said Matthew Porteus, MD, PhD, Principal Investigator at Stanford School of Medicine. "Their product allows us to quickly evaluate, in a cost-effective manner, the best guide RNA to stimulate genome editing, including by homologous recombination, in therapeutically relevant human stem cells and primary human T-cells.  My team has also found that they deliver excellent customer service and are willing to work closely with us in terms of addressing our experimental needs. I highly recommend them."

Andrew Scharenberg’s Lab at Seattle Children’s Research Institute (affiliated with the University of Washington) has also been a pioneer in applying gene editing technologies towards hemoglobinopathies and immunodeficiencies. Researchers there are utilizing Synthego’s modified sgRNA for their work in CRISPR editing T-cells and stem cells, seeing editing efficiencies of up to 90 percent.

"Synthego’s chemically modified sgRNA provides a critical tool for our CRISPR research when it comes to difficult stem cell gene targets," said Andrew Scharenberg, MD, Principal Investigator at Seattle Children’s Research Institute. "Our research into stem cell-based human therapeutics presents editing challenges that require the highest efficiency guides."

Synthego is the first company in the world to be able to offer modified synthetic sgRNA at a nanomole scale and at a price point that is practical to stem cell and CRISPR therapeutic researchers. Previous sources of modified synthetic sgRNA cost up to 5X more and took up to 8 weeks to ship. Synthego is able to ship the modified synthetic sgRNA in as little as 5 days.

Organizations conducting research related to CRISPR therapeutics, stem cells, immunotherapies, or encountering challenges with editing efficiencies should consider modified synthetic sgRNA for CRISPR genome editing. In addition, chemically modified sgRNA may aid in editing challenging targets even in common cell lines, and can provide protection against exonucleases in prokaryotic cells.

Modified guides are available as an option to the entire CRISPRevolution synthetic RNA portfolio.

For more information visit: www.synthego.com.