Nucleic Acids therapeutics using PolyPurine Reverse Hoogsteen hairpins.

Nucleic Acids therapeutics using PolyPurine Reverse Hoogsteen hairpins. Biochem Pharmacol. 2020 Dec 15;:114371 Authors: Noé V, Aubets E, Félix AJ, Ciudad CJ Abstract PolyPurine Reverse Hoogsteen hairpins (PPRHs) are DNA hairpins formed by intramolecular reverse Hoogsteen bonds which can bind to polypyrimidine stretches in dsDNA by Watson:Crick bonds, thus forming a triplex and displacing the fourth strand of the genomic DNA. PPRHs were first described as a gene silencing tool in vitro for DHFR, telomerase and survivin genes. Then, the effect of PPRHs directed against the survivin gene was also determined in vivo using a xenograft model of prostate cancer cells (PC3). Since then, the ability of PPRHs to inhibit gene expression has been explored in other genes involved in cancer (BCL-2, mTOR, topoisomerase, C-MYC and MDM2), in immunotherapy (SIRPα/CD47 and PD-1/PD-L1 tandem) or in replication stress (WEE1 and CHK1). Furthermore, PPRHs have the ability to target the complementary strand of a G-quadruplex motif as a regulatory element of the TYMS gene. PPRHs have also the potential to correct point mutations in the DNA as shown in two collections of CHO cell lines bearing mutations in either the dhfr or aprt loci. Finally, based on the capability of PPRHs to form triplexes, they have been incorporated as probes in biosensors for the determination of the DNAmethylation status of PAX-5 in cancer and the detection of mtLSU rRNA for the d...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research