Source of Nucleic-Acid Asymmetry May Advance Gene Therapy

Research from the Institute for Research in Biomedicine (IRB Barcelona) published in the journal CHEM offers insight into the source of asymmetry between nucleic acid hybrids. This development may prove to be an important contribution to improving gene therapies.

The study, done in collaboration with the Centre for Genomic Regulation and the Institute for Advanced Chemistry of Catalonia, has analyzed the source and biological consequences of the asymmetry that occurs in RNA–DNA hybrids when the relation between purine (adenine and guanine) and pyrimidine (thymine and cytosine or uracil) bases differs in RNA and DNA strands (2).

According to the researchers, the results of the study indicate that in contrast to the homoduplexes of DNA or RNA, RNA–DNA hybrids show intrinsic asymmetry, which suggests that this property is important for biological function and for biotechnological applications. When the DNA of the hybrids is rich in pyrimidine bases, the duplex is more stable and rigid than when the DNA chain is rich in purine bases. This symmetry, according to the researchers, may lead to improvements in the efficiency of therapies based on hybrids, such as antisense therapy, which can, for instance, control the regulation of genes that contribute to the progress of cancer progression and other diseases, as well as CRISPR-Cas9 gene-editing technology, which allows a target gene to be cut and edited.

“Thanks to a combination of theoretical and experimental methods, we have been able to understand the relationship between the sequence and stability of DNA–RNA hybrids-structures that form in the cell spontaneously and that have enormous therapeutic potential,” said Modesto Orozco, head of the Molecular Modeling and Bioinformatics Laboratory at IRB Barcelona and senior professor at the University of Barcelona, in an institute press release. 

“Our results will allow further development of much more efficient methods to block and edit genes and that can potentially become therapeutic alternatives for diseases for which there are no effective treatments.”

Source: IRB Barcelona