TY - JOUR

T1 - Split–Combine Click-SELEX Reveals Ligands Recognizing the Transplant Rejection Biomarker CXCL9

AU - Siegl, Julia

AU - Nikolin, Christoph

AU - Phung, Ngoc Linh

AU - Thoms, Stefanie

AU - Blume, Cornelia

AU - Mayer, Günter

N1 - Funding Information: This work was made possible by fund from the Federal Ministry of Economic Affairs and Energy to G.M. and C.B. (ZF 4613701CR8) and the German Research Foundation (DFG, MA3442/7-1) and the European Regional Development Fund (85006385) to C.B. We thank I. Förster for sharing aliquots of the various chemokines used for specificity testing.

PY - 2022/1/21

Y1 - 2022/1/21

N2 - Renal rejection is a major incidence in patients after kidney transplantation and associated with allograft scarring and function loss, especially in antibody-mediated rejection. Regular clinical monitoring of kidney-transplanted patients is thus necessary, but measuring donor-specific antibodies is not always predictive, and graft biopsies are time-consuming and costly and may come up with a histological result unsuspicious for rejection. Therefore, a noninvasive diagnostic approach to estimate an increased probability of kidney graft rejection by measuring specific biomarkers is highly desired. The chemokine CXCL9 is described as an early indicator of rejection. In this work, we identified clickmers and an aptamer by split–combine click-SELEX (systematic evolution of ligands by exponential enrichment) that bind CXLC9 with high affinity. The aptamers recognize native CXCL9 and maintain binding properties under urine conditions. These features render the molecules as potential binding and detector probes for developing point-of-care devices, e.g., lateral flow assays, enabling the noninvasive monitoring of CXCL9 in renal allograft patients.

AB - Renal rejection is a major incidence in patients after kidney transplantation and associated with allograft scarring and function loss, especially in antibody-mediated rejection. Regular clinical monitoring of kidney-transplanted patients is thus necessary, but measuring donor-specific antibodies is not always predictive, and graft biopsies are time-consuming and costly and may come up with a histological result unsuspicious for rejection. Therefore, a noninvasive diagnostic approach to estimate an increased probability of kidney graft rejection by measuring specific biomarkers is highly desired. The chemokine CXCL9 is described as an early indicator of rejection. In this work, we identified clickmers and an aptamer by split–combine click-SELEX (systematic evolution of ligands by exponential enrichment) that bind CXLC9 with high affinity. The aptamers recognize native CXCL9 and maintain binding properties under urine conditions. These features render the molecules as potential binding and detector probes for developing point-of-care devices, e.g., lateral flow assays, enabling the noninvasive monitoring of CXCL9 in renal allograft patients.

UR - http://www.scopus.com/inward/record.url?scp=85123368672&partnerID=8YFLogxK

U2 - 10.1021/acschembio.1c00789

DO - 10.1021/acschembio.1c00789

M3 - Article

C2 - 35018777

AN - SCOPUS:85123368672

VL - 17

SP - 129

EP - 137

JO - ACS chemical biology

JF - ACS chemical biology

SN - 1554-8929

IS - 1

ER -