DataVXACS Applied Materials & InterfacesPaper
journal article·2023-03-15

Engineering Circular Aptamer Assemblies with Tunable Selectivity to Cell Membrane Antigens In Vitro and In Vivo

Liqing Qi, Yuan Tian, Na Li, Menghan Mao, Xiaohong Fang, Da Han

ACS Applied Materials & Interfaces· Volume 15· Issue 10
Publisher page
Source abstract

Abstract

The strategy of enhancing molecular recognition by improving the binding affinity of drug molecules against targets has generated a lot of successful therapeutic applications. However, one critical consequence of such affinity improvement, generally called “on-target, off-tumor” toxicity, emerged as a major obstacle limiting their clinical usage. Herein, we provide a modular assembly strategy that affords affinity-tunable DNA nanostructures allowing for immobilizing multiple aptamers that bind to the example antigen of EpCAM with different affinities. We develop a theoretical model proving that the apparent affinity of aptamer assemblies to target cells varies with antigen density as well as aptamer valency. More importantly, we demonstrate experimentally that the theoretical model can be used to predict the least valency required for discrimination between EpCAM high and EpCAM low cells in vitro and in vivo . We believe that our strategy will have broad applications in an engineering nucleic acid-based delivery platform for targeted and cell therapy.
Source: openalex_inverted_index · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Advanced biosensing and bioanalysis techniques · RNA Interference and Gene Delivery · CAR-T cell therapy research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, School of Medicine, Shanghai Jiao Tong University, Renji Hospital, Institute of Molecular Medicine, Shanghai 200127, China

Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China

National Genomics Data Center, China National Center for Bioinformation, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China

Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China

Funding

Ministry of Science and Technology of the People's Republic of China · National Natural Science Foundation of China · Shanghai Rising-Star Program · Innovative Research Team of High-Level Local University in Shanghai

References (36)

Show source-provided references
1. 10.1038/mt.2010.2410.1038/mt.2010.24 ↗
2. 10.1158/2326-6066.CIR-17-021110.1158/2326-6066.CIR-17-0211 ↗
3. 10.1073/pnas.110535110810.1073/pnas.1105351108 ↗
4. 10.1073/pnas.200396811710.1073/pnas.2003968117 ↗
5. Curk T. · Multivalency: Concepts, Research & Applications · 2017 · 7510.1002/9781119143505.ch3 ↗
6. Csizmar C. M. · J. Am. Chem. Soc. · 2019 · 141 · 25110.1021/jacs.8b09198 ↗
7. 10.1039/c3sc52986j10.1039/c3sc52986j ↗
8. 10.1158/0008-5472.CAN-15-013910.1158/0008-5472.CAN-15-0139 ↗
9. 10.1158/0008-5472.CAN-15-015910.1158/0008-5472.CAN-15-0159 ↗
10. 10.1016/j.chembiol.2006.11.01510.1016/j.chembiol.2006.11.015 ↗
11. 10.1021/cb400258d10.1021/cb400258d ↗
12. 10.1039/D0SC01127D10.1039/D0SC01127D ↗
13. 10.1002/tcr.20210033310.1002/tcr.202100333 ↗
14. 10.1039/D0SC03584J10.1039/D0SC03584J ↗
15. Agarwal S. · Nat. Commun. · 2021 · 12 · 110.1038/s41467-020-20314-w ↗
16. 10.1093/nar/gkz105610.1093/nar/gkz1056 ↗
17. 10.1002/adfm.20210972810.1002/adfm.202109728 ↗
18. 10.1002/adma.20220173110.1002/adma.202201731 ↗
19. 10.1038/s41413-022-00212-110.1038/s41413-022-00212-1 ↗
20. 10.1016/j.bbagen.2018.07.02910.1016/j.bbagen.2018.07.029 ↗
21. 10.1016/j.biotechadv.2021.10790210.1016/j.biotechadv.2021.107902 ↗
22. Zhang H. · Sci. Rep. · 2015 · 5 · 1
23. 10.1021/acs.analchem.0c0364310.1021/acs.analchem.0c03643 ↗
24. 10.1021/acs.nanolett.2c0337710.1021/acs.nanolett.2c03377 ↗
25. 10.1038/s41467-022-31684-810.1038/s41467-022-31684-8 ↗
26. 10.1021/acs.analchem.2c0164610.1021/acs.analchem.2c01646 ↗
27. Mao, M.; Lin, Z.; Chen, L.; Zou, Z.; Zhang, J.; Dou, Q.; Wu, J.; Chen, J.; Wu, M.; Niu, L. Modular DNA-origami-based nanoarrays enhanced cell binding-affinity through “lock-key” interaction. 2022.10.21203/rs.3.rs-2148903/v1 ↗
28. 10.1002/adma.20170365810.1002/adma.201703658 ↗
29. 10.1038/s41565-020-0719-010.1038/s41565-020-0719-0 ↗
30. 10.1021/ja104702q10.1021/ja104702q ↗
31. 10.1038/s41467-020-20638-710.1038/s41467-020-20638-7 ↗
32. 10.3184/146867818X1531990382916410.3184/146867818X15319903829164 ↗
33. 10.1021/ac400366b10.1021/ac400366b ↗
34. 10.1093/nar/gkq99610.1093/nar/gkq996 ↗
35. Hu Q. · Chem. Rev. · 2019 · 119 · 645910.1021/acs.chemrev.7b00663 ↗
36. 10.3390/cancers1003008010.3390/cancers10030080 ↗