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Abstract

GENE THERAPY Reactions ShareShare onFacebookTwitterWechatLinked InRedditEmail C&EN, 2023, 101 (18), p 3June 5, 2023Cite this:C&EN 101, 18, 3(Credit: C&EN)Figure1of2(Credit: C&EN)Figure1of2Letters to the editorPeptide nucleic acids targeting noncanonical DNA and RNAAs a molecular biologist, I always enjoy reading articles concerning DNA and RNA. Your excellent article in the April 3, 2023, issue of C&EN (page 18) titled “The Promise of Peptide Nucleic Acids” discussed an important topic relating to gene therapy—that is, antisense therapeutics and gene- editing tools. Peptide nucleic acids (PNAs) can open a double-stranded (ds) DNA molecule and inhibit its gene expression. PNAs bind to DNA and RNA with high specificity and selectivity, resulting in PNA-DNA and PNA-RNA hybrid structures. Therefore, they have exciting potential as diagnostic tools and therapeutic agents.However, only briefly discussed in the article is the possibility of developing PNAs to target nucleic acid secondary structures such as RNA hairpins. More focus needs to be placed on all the other nucleic acid secondary structures, going beyond canonical right-handed ds-B-DNA, right-handed ds-A-RNA, and single-stranded (such as messenger RNA) nucleic acids based on nucleotide sequences—that is, the hybridization of base pairs.Researchers need to consider targeting exotic, noncanonical nucleic acids—that is, alternative and multistranded DNA and RNA structures. Local transitions in the structure of canonical ds-B-DNA are functionally significant biological molecules, regulating many cellular processes, such as transcription and translation. These exotic nucleic acid structures have also been connected to genetic instability in the presence or deficiency of DNA damage, with or without DNA replication. DNA and RNA possess dynamic structural variability resulting in a variety of unusual nucleic acid structures, such as cruciform DNA, DNA-RNA hybrids, slipped-strand DNA, and parallel-stranded DNA.Expanding the therapeutic capabilities of PNAs beyond canonical B-DNA would expand PNAs’ use in therapeutics. The expansion should include alternative ds-DNA structures such as left-handed ds-Z-DNA and left-handed ds-Z-RNA. It should also include multistranded DNA structures such as triplex DNA (intermolecular and intramolecular, like H-DNA), G4-quadruplex DNA, and i-motif DNA.If possible, targeting noncanonical nucleic acid structures with PNAs would increase the chance of developing novel therapeutics that can target all genomic DNA and RNA structures in genes and telomeres. We are witnessing the transition of gene medicine from an experimental technology into a real-world, practical approach for developing nucleic acid–based therapeutics, such as used for gene silencing or gene editing (like CRISPR) of pathological conditions.Using PNAs as therapeutic tools for targeting both canonical and noncanonical nucleic acids will allow for their full potential and optimal expansion of gene therapy.Claude GagnaBronxville, New YorkRecognizing nitrogen-fixing bacteria’s potential to reduce fertilizer useIn the article titled “Growing More Food with Less Chemicals,” which appeared in the May 8, 2023, issue of C&EN (page 28), there was a glaring omission.What was left out was the research and development of genetically modified nitrogen-fixing bacteria that can be applied to seed, foliage, or soil to reduce fertilizer use.Herbert B. ScherMoraga, California