"Nature" Interpretation of the working principle of DNAzymes in cells

A DNAzyme (red) uses its binding arm to dock at a specific position on the RNA strand (yellow) and then cleave it at its core

DNAzymes (DNAzymes ) DNAzymes are a precise biological catalyst that can destroy unwanted RNA molecules

DNAzymes-a word composed of DNA and enzymes-are DNA sequences with catalytic activity

Its purpose is to target unwanted RNA molecules in viruses, cancers or damaged nerve cells, using DNAzymes to attack and destroy them

The benefits of this therapy are obvious: unwanted RNA can be precisely destroyed, while other useful RNA strands in the cell remain intact

Dr.

In their research, authors from HHU and a team from the Jülich Research Center (FZJ), the University of Bonn, and a Swiss company tried to understand how the system as a whole works dynamically, and what steps take place in the process of combining and disintegrating.

The researchers observed this process at atomic resolution and performed some real-time observations using a high-resolution nuclear magnetic resonance (NMR) spectrometer

The team of Professor Holger Gohlke, Chairman of HHU Pharmaceutical and Medicinal Chemistry and FZJ Institute of Biological and Earth Sciences conducted molecular dynamics simulations of DNAzyme/RNA complexes, adding: “In the sense of the best integrated modeling, we can propose atomic The level of reliable RNA cleavage mechanism, and provides information on the RNA base preference at the cleavage site

Jan Borggräfe, a PhD researcher in the Etzkorn working group and the lead author of the study, explained why DNAzymes do not work well in cells: "We have identified magnesium as a key cofactor, which plays a variety of important roles in this mechanism, but it The binding to DNAzyme is relatively poor, and it only binds briefly

The next step is to conduct structural studies on cell culture and organoids

Dr.

Professor Dieter Willbold, Director of the Harvard Institute of Physical Biology and FZJ Institute of Structural Biochemistry, added: "This research is yet another example of how fundamental research in structural biology can provide an important contribution to breakthrough biomedical progress

References: “Time-resolved structural analysis of an RNA-cleaving DNA catalyst” by Jan Borggräfe, Julian Victor, Hannah Rosenbach, Aldino Viegas, Christoph GW Gertzen, Christine Wuebben, Helena Kovacs, Mohanraj Gopalswamy, Detlev Riesner, Gerhard Steger, Olav Schiemann, Holger Gohlke, Ingrid Span and Manuel Etzkorn, 23 December 2021, Nature .