Advances in peptide nucleic acid-based sensors and antisense therapeutics: Surface immobilization on planar gold substrates

Peptide nucleic acids (PNAs) are synthetic analogues of nucleic acids featuring a neutral peptide-backbone that provides exceptional stability and resistance to enzymatic degradation. They are highly specific towards complementary DNA or RNA sequences rendering them ideal capture probes for sensitive and selective biosensing. The uncharged backbone minimizes nonspecific interactions and reduces background noise in bioelectronic devices, thereby improving signal-to-noise ratios. The precise immobilization of PNAs on gold substrates allows the development of real-time, label-free electrochemical and optical sensors. Parameters - such as immobilization strategy, concentration, temperature, substrate morphology - that strongly influences the surface probe density and ultimately play key roles in the sensor's performance are discussed within this review. Furthermore, this review highlights current strategies for tuning planar gold-based PNA sensors and outlines how nucleic acid sensor technologies can be leveraged to evaluate emerging PNA-based antisense oligonucleotides. Given the relevance of PNA derivatives in therapeutic oligonucleotide development, it further shows how sensor platforms can be used to assess and improve the design and binding kinetics of new PNA antisense drug candidates.