Aptamers without SELEX:
- 1Xelari Inc., 8 The Green B, Dover, DE 19901, USA; Corresponding author: Vladislava A. Dolgusheva, Xelari Inc., 8 The Green B, Dover, DE 19901, USA.
- 2Xelari Inc., 8 The Green B, Dover, DE 19901, USA
- 3Mad Devs LLC, 103 Ibraimova str., Bishkek 720011, Kyrgyzstan
Abstract
Systematic evolution of ligands by exponential enrichment (SELEX)-based aptamer discovery can be constrained by target availability, selection biases, and optimization requirements. We introduce Xelari, a modular pipeline for de novo DNA and RNA aptamer design from protein structures without target-specific SELEX data or retraining. Xelari combines algorithmic modules with surrogate models trained on physical or structural references. InNA reproduced nucleotide-amino-acid interaction energies with RMSE of 0.19 kcal/mol across 483,735 reference pairs. AliNA achieved a mean F1 of 0.757 on 339 PDB-derived RNA evaluation sequences. Edgar correlated with experimental folding energies but did not reproduce their absolute scale, supporting its use as a ranking heuristic. Under the reported calibration, ValentiNA showed MAE of 0.931 kcal/mol and Spearman ρ of 0.795 across 32 retrospective records associated with 27 structural templates; this analysis does not establish family-independent validation. Prospectively, three DNA aptamers designed against Treponema pallidum protein structures showed cell-associated binding in a treponeme assay (apparent K D , 0.91–2.57 μM). A fourth DNA aptamer served as a capture reagent in a serum-based hybrid aptamer-antibody assay for Tau441. These applications support feasibility without establishing intended-target engagement in the cellular assay or a general success rate, positioning structure-based design as a complement to experimental selection.
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BibTeX
@article{dolgusheva2026aptamers,
title = {{Aptamers without SELEX:}},
author = {Vladislava A. Dolgusheva and Iosif V. Leibin and Natalia O. Kudryashova and Artem R. Mukanov and Ivan I. Kuznetsov and Artem L. Manasyan and Gleb A. Pavlyuk and Ivan V. Mishkorez and Anna M. Keremet and Pavel R. Podlesnyi and Alexey N. Kalinkin and Kirill S. Avdeev and Maxim D. Kuznetsov and Nikita O. Parfenov and Stanislav M. Gromov and Dmitry Ufaev and Shamsudin S. Nasaev},
journal = {Molecular Therapy: Nucleic Acids},
year = {2026},
month = oct,
doi = {10.1016/j.omtn.2026.103133},
url = {https://doi.org/10.1016/j.omtn.2026.103133},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Aptamers without SELEX:
AU - Vladislava A. Dolgusheva
AU - Iosif V. Leibin
AU - Natalia O. Kudryashova
AU - Artem R. Mukanov
AU - Ivan I. Kuznetsov
AU - Artem L. Manasyan
AU - Gleb A. Pavlyuk
AU - Ivan V. Mishkorez
AU - Anna M. Keremet
AU - Pavel R. Podlesnyi
AU - Alexey N. Kalinkin
AU - Kirill S. Avdeev
AU - Maxim D. Kuznetsov
AU - Nikita O. Parfenov
AU - Stanislav M. Gromov
AU - Dmitry Ufaev
AU - Shamsudin S. Nasaev
PY - 2026
DA - 2026/10/07
JO - Molecular Therapy: Nucleic Acids
DO - 10.1016/j.omtn.2026.103133
UR - https://doi.org/10.1016/j.omtn.2026.103133
AB - Systematic evolution of ligands by exponential enrichment (SELEX)-based aptamer discovery can be constrained by target availability, selection biases, and optimization requirements. We introduce Xelari, a modular pipeline for de novo DNA and RNA aptamer design from protein structures without target-specific SELEX data or retraining. Xelari combines algorithmic modules with surrogate models trained on physical or structural references. InNA reproduced nucleotide-amino-acid interaction energies with RMSE of 0.19 kcal/mol across 483,735 reference pairs. AliNA achieved a mean F1 of 0.757 on 339 PDB-derived RNA evaluation sequences. Edgar correlated with experimental folding energies but did not reproduce their absolute scale, supporting its use as a ranking heuristic. Under the reported calibration, ValentiNA showed MAE of 0.931 kcal/mol and Spearman ρ of 0.795 across 32 retrospective records associated with 27 structural templates; this analysis does not establish family-independent validation. Prospectively, three DNA aptamers designed against Treponema pallidum protein structures showed cell-associated binding in a treponeme assay (apparent K D , 0.91–2.57 μM). A fourth DNA aptamer served as a capture reagent in a serum-based hybrid aptamer-antibody assay for Tau441. These applications support feasibility without establishing intended-target engagement in the cellular assay or a general success rate, positioning structure-based design as a complement to experimental selection.
SN - 2162-2531
ER -