Based on the pioneering exploration and significant progress in nanopore glycan sequencing, researchers Dr. Gao Zhaobing and Associate Researcher Xia Bingqing from the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, were invited to provide an outlook on the development and application prospects of nanopore glycan sequencing. They presented a design scheme for nanopore glycan sequencers and, for the first time, systematically proposed a possible roadmap for nanopore glycan sequencing. Their related review was published in "Chemical Science."
The precise analysis of glycan structures is fundamental for studying the mechanisms of glycan involvement in life processes and for the development of glycan-based drugs. However, inefficient and costly methods for glycan structure analysis have hindered the progress of glycan science. Due to numerous technical bottlenecks, "glycan sequencing" is considered the "pearl on the crown" of glycan research. Nanopore technology can provide sequence information of analytes at the single-molecule level with high sensitivity and spatiotemporal resolution. Over the past few decades, nanopore technology has made revolutionary breakthroughs in nucleic acid and protein sequence analysis or structural identification, offering great promise for glycan sequencing.
In their earlier research, the team of Gao Zhaobing and Xia Bingqing used biological nanopores to create a fingerprint library of glycan functional groups, advancing glycan research from "glycan detection" to "glycan sequencing." Furthermore, they achieved the first-ever sequence identification of complex polysaccharides using biological nanopores, enabling the resolution of complex polysaccharides at the monosaccharide scale with chain lengths of up to 10 units.
The current status and trends in nanopore glycan sensing research indicate the feasibility of nanopore glycan sequencing. The collaborative team at the Shanghai Institute of Materia Medica proposed three potential feasible nanopore glycan sequencing technology roadmaps: chain sequencing, hydrolysis sequencing, and splicing sequencing. The different sequencing principles of each technology roadmap determine their unique advantages and limitations.
Nanopore Sugar Sequencing Technology Roadmap. Image source: "Chemical Science."
The article points out that efficient analysis of sugar sequences will help in-depth research on the relationship between sugar molecular structure and function, as well as related physiological and pathological processes. It will also promote the discovery of sugar-related disease markers. Nanopore sugar sequencers are expected to be used in diagnosing clinically relevant diseases involving sugars. The advancement of sugar sequencing technology will further drive progress in sugar science and even the entire field of life sciences. The research team emphasizes that the continued development of nanopore sugar sequencing relies on interdisciplinary collaboration in ion channel technology, sugar chemistry, glycobiology, and other related fields.
Related paper information: https://doi.org/10.1039/D4SC01466A
