Sequence-Specific Targeting of Duplex DNA by Peptide Nucleic Acids via Triplex Strand Invasion

Methods ◽  
2001 ◽  
Vol 23 (2) ◽  
pp. 108-122 ◽  
Author(s):  
Vadim V. Demidov ◽  
Maxim D. Frank-Kamenetskii
Keyword(s):  
Nucleic Acids ◽  
Peptide Nucleic Acids ◽  
Duplex Dna ◽  
Specific Targeting ◽  
Strand Invasion

scholarly journals Duplex DNA-Invading γ-Modified Peptide Nucleic Acids Enable Rapid Identification of Bloodstream Infections in Whole Blood

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Jörk Nölling ◽  
Srinivas Rapireddy ◽  
Joel I. Amburg ◽  
Elizabeth M. Crawford ◽  
Ranjit A. Prakash ◽  
...  
Keyword(s):  
Blood Culture ◽  
Nucleic Acids ◽  
Fungal Pathogens ◽  
Peptide Nucleic Acids ◽  
Unmet Need ◽  
Bloodstream Infections ◽  
Rapid Identification ◽  
Duplex Dna ◽  
Diagnostic Approaches ◽  
Antimicrobial Intervention

ABSTRACT Bloodstream infections are a leading cause of morbidity and mortality. Early and targeted antimicrobial intervention is lifesaving, yet current diagnostic approaches fail to provide actionable information within a clinically viable time frame due to their reliance on blood culturing. Here, we present a novel pathogen identification (PID) platform that features the use of duplex DNA-invading γ-modified peptide nucleic acids (γPNAs) for the rapid identification of bacterial and fungal pathogens directly from blood, without culturing. The PID platform provides species-level information in under 2.5 hours while reaching single-CFU-per-milliliter sensitivity across the entire 21-pathogen panel. The clinical utility of the PID platform was demonstrated through assessment of 61 clinical specimens, which showed >95% sensitivity and >90% overall correlation to blood culture findings. This rapid γPNA-based platform promises to improve patient care by enabling the administration of a targeted first-line antimicrobial intervention. IMPORTANCE Bloodstream infections continue to be a major cause of death for hospitalized patients, despite significant improvements in both the availability of treatment options as well their application. Since early and targeted antimicrobial intervention is one of the prime determinants of patient outcome, the rapid identification of the pathogen can be lifesaving. Unfortunately, current diagnostic approaches for identifying these infections all rely on time-consuming blood culture, which precludes immediate intervention with a targeted antimicrobial. To address this, we have developed and characterized a new and comprehensive methodology, from patient specimen to result, for the rapid identification of both bacterial and fungal pathogens without the need for culturing. We anticipate broad interest in our work, given the novelty of our technical approach combined with an immense unmet need.

scholarly journals Kinetic analysis of specificity of duplex DNA targeting by homopyrimidine peptide nucleic acids

1997 ◽  
Vol 72 (6) ◽  
pp. 2763-2769 ◽  
Author(s):  
V.V. Demidov ◽  
M.V. Yavnilovich ◽  
M.D. Frank-Kamenetskii
Keyword(s):  
Nucleic Acids ◽  
Kinetic Analysis ◽  
Peptide Nucleic Acids ◽  
Duplex Dna ◽  
Dna Targeting
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