Decoding the source of asymmetry in DNA - RNA hybrids to improve gene therapy efficiency

The asymmetry of DNA-RNA hybrids can be used to improve the efficiency of gene editing technologies like CRISPR-Cas9 technique. Image: M. Terrazas, IRB Barcelona
The asymmetry of DNA-RNA hybrids can be used to improve the efficiency of gene editing technologies like CRISPR-Cas9 technique. Image: M. Terrazas, IRB Barcelona
Research
(14/06/2019)

A study published in the journal CHEM furthers the understanding on the asymmetry between nucleic acid hybrids and gives new perspectives to promote the efficiency of genic therapies that can be applied in several pathologies.


Through a combination of protocols and experiments, “we could understand the relation between sequencing and RNA-DNA hybrid stability, structures that are spontaneously formed in the cell with a great therapeutic potential”, says Modesto Orozco, professor at the Department of Biochemistry and Molecular Biomedicine of the Faculty of Chemistry of the UB. 
 

The asymmetry of DNA-RNA hybrids can be used to improve the efficiency of gene editing technologies like CRISPR-Cas9 technique. Image: M. Terrazas, IRB Barcelona
The asymmetry of DNA-RNA hybrids can be used to improve the efficiency of gene editing technologies like CRISPR-Cas9 technique. Image: M. Terrazas, IRB Barcelona
Research
14/06/2019

A study published in the journal CHEM furthers the understanding on the asymmetry between nucleic acid hybrids and gives new perspectives to promote the efficiency of genic therapies that can be applied in several pathologies.


Through a combination of protocols and experiments, “we could understand the relation between sequencing and RNA-DNA hybrid stability, structures that are spontaneously formed in the cell with a great therapeutic potential”, says Modesto Orozco, professor at the Department of Biochemistry and Molecular Biomedicine of the Faculty of Chemistry of the UB. 
 

“Our results will enable us to progress in the development of blocking and gene editing methods which are more efficient and could become therapeutic alternatives for diseases which are considered orphan”, says Orozco, head of the Molecular Modelling and Bioinformatics Laboratory of IRB Barcelona and member of the Bioinformatics Barcelona (BIB) platform.


The new study analyses the source and biological consequences of the asymmetry that occurs in hybrid RNA-DNA structures when the relation between purine bases (adenine and guanine) and pyrimidine (thymine and cytosine or uracil) bases differ in RNA and DNA strands. In particular, when hybrid DNA is rich in pyrimidine bases, the duplex structure is more stable and rigid than when it is rich in purine bases. Other participants in the study are the teams of the Center for Genomic Regulation (CRG) and the Institute for Advanced Chemistry of Catalonia (IQAC-CSIC).

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