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Cited by 533Advanced biosensing and bioanalysis techniquesDNA and Nucleic Acid ChemistryRNA and protein synthesis mechanisms

Nucleic Acid Ligands With Protein-like Side Chains: Modified Aptamers and Their Use as Diagnostic and Therapeutic Agents

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Rohloff, John C, Gelinas, Amy D, Jarvis, Thale C, Ochsner, Urs A, Schneider, Daniel J, Gold, Larry, Janjic, Nebojsa·2014·Molecular Therapy - Nucleic Acids
DOI 10.1038/mtna.2014.49PMC PMC4217074
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Abstract

Limited chemical diversity of nucleic acid libraries has long been suspected to be a major constraining factor in the overall success of SELEX (Systematic Evolution of Ligands by EXponential enrichment). Despite this constraint, SELEX has enjoyed considerable success over the past quarter of a century as a result of the enormous size of starting libraries and conformational richness of nucleic acids. With judicious introduction of functional groups absent in natural nucleic acids, the "diversity gap" between nucleic acid-based ligands and protein-based ligands can be substantially bridged, to generate a new class of ligands that represent the best of both worlds. We have explored the effect of various functional groups at the 5-position of uracil and found that hydrophobic aromatic side chains have the most profound influence on the success rate of SELEX and allow the identification of ligands with very low dissociation rate constants (named Slow Off-rate Modified Aptamers or SOMAmers). Such modified nucleotides create unique intramolecular motifs and make direct contacts with proteins. Importantly, SOMAmers engage their protein targets with surfaces that have significantly more hydrophobic character compared with conventional aptamers, thereby increasing the range of epitopes that are available for binding. These improvements have enabled us to build a collection of SOMAmers to over 3,000 human proteins encompassing major families such as growth factors, cytokines, enzymes, hormones, and receptors, with additional SOMAmers aimed at pathogen and rodent proteins. Such a large and growing collection of exquisite affinity reagents expands the scope of possible applications in diagnostics and therapeutics.

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  • The SomaScan assay uses DNA-based slow off-rate modified aptamers (SOMAmer reagents) to quantify the relative abundance of approximately 7000 proteins with high specificity and limits of detection largely comparable to antibody-based assays.

    “The assay uses DNA-based slow off-rate modified aptamers (SOMAmerTM reagents) to quantify the relative abundance of approximately 7000 proteins with high specificity and limits of detection largely comparable to antibody-based assays.”

    From Cross-ancestry comparison of aptamer and antibody protein measures (2026) · cites this paper as [51]

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Cited by

Sorted by citations

Authors
Rohloff, J. C., Gelinas, A. D., Jarvis, T. C., Ochsner, U. A., Schneider, D. J., Gold, L., & Janjic, N.
Affiliations
SomaLogic (United States) (US)
ORCID
Venue
Molecular Therapy - Nucleic Acids
Publisher
Elsevier BV
Published
2014-01
Volume
3
Pages
e201
ISSN
2162-2531 (ISSN-L)
DOI
10.1038/mtna.2014.49
PMC
PMC4217074
OpenAlex
W2066356596
Cited by
533
References
6
Citations by year
2026: 35 · 2025: 54 · 2024: 53 · 2023: 42 · 2022: 58 · 2021: 48 · 2020: 58 · 2019: 36 · 2018: 52 · 2017: 44 · 2016: 34 · 2015: 19
FWCI
3.04
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Therapy — Nucleic Acids (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
SOMAmer, nucleic acid ligands, SELEX, nucleotide modification, protein binding, affinity reagents, diagnostic agents, therapeutic agents

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