Optimizing Production of Chemically Modified sgRNA with High Quality

Dr. Songjun Xiao, PhD, process development senior scientist at LGC Axolabs
Ingo Röhl, PhD, Managing Director Analytics at Axolabs

Optimizing Production of Chemically Modified sgRNA with High Quality

Click to watch video

The therapeutic potential of nucleic acids, ranging from antisense oligonucleotides (ASO) to messenger RNA (mRNA), remains a subject of continuous interest. CRISPR-Cas9 gene-editing technology has revolutionized gene therapeutics, with the landmark approval of CRISPR-Cas therapy in December 2023 for sickle cell disease. CRISPR-Cas9 relies on single guide RNA (sgRNA) to precisely target genomic sites, inducing DNA strand breaks subsequently repaired by cellular mechanisms. While in vitro transcription (IVT) can generate sgRNA, chemically modified sgRNAs not only enhance editing efficiency but also enable scalable production and the flexible design of sgRNA sequences. Despite the advantages of solid-phase synthesis in sgRNA production, challenges persist due to their length and instability.

Dr. Songjun Xiao's research interests lie in the highly interdisciplinary field of bioorganic chemistry, with a particular focus on nucleic acid chemistry, bioconjugation, sequencing, and genomics. He earned his Ph.D. from the University of Maryland in 2020 under the mentorship of Prof. Jeff Davis, where his research concentrated on nucleoside chemistry and supramolecular chemistry. Following this, he conducted postdoctoral research at the University of Utah in Prof. Cindy Burrows' lab, specializing in DNA/RNA damage and modification sequencing. Since joining LGC Axolabs in 2022 as a process development scientist, Songjun has been dedicated to the production and optimization of sgRNA and other nucleic acid therapeutics. Beyond his professional pursuits, he finds enjoyment in traveling and playing and watching tennis in his leisure time.