DNA recognition and induced genome modification by a hydroxymethyl-γ tail-clamp peptide nucleic acid
Source abstract
Abstract
Peptide nucleic acids (PNAs) can target and stimulate recombination reactions in genomic DNA. We have reported that γPNA oligomers possessing the diethylene glycol γ-substituent show improved efficacy over unmodified PNAs in stimulating recombination-induced gene modification. However, this structural modification poses a challenge because of the inherent racemization risk in O-alkylation of the precursory serine side chain. To circumvent this risk and improve γPNA accessibility, we explore the utility of γPNA oligomers possessing the hydroxymethyl-γ moiety for gene-editing applications. We demonstrate that a γPNA oligomer possessing the hydroxymethyl modification, despite weaker preorganization, retains the ability to form a hybrid with the double-stranded DNA target of comparable stability and with higher affinity than that of the diethylene glycol-γPNA. When formulated into poly(lactic-co-glycolic acid) nanoparticles, the hydroxymethyl-γPNA stimulates higher frequencies (≥1.5-fold) of gene modification than the diethylene glycol γPNA in mouse bone marrow cells.
Source: openalex_inverted_index · Quality: baseline
Research context
OpenAlex topics: Advanced biosensing and bioanalysis techniques · RNA Interference and Gene Delivery · DNA and Nucleic Acid Chemistry
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (55)
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