DataVXACS Applied Materials & InterfacesPaper
journal article·2020-10-28

An All-in-One Nanomedicine Consisting of CRISPR-Cas9 and an Autoantigen Peptide for Restoring Specific Immune Tolerance

Ying-Li Luo, Li-Fang Liang, Yun-Jiu Gan, Jing Liu, Yue Zhang, Ya-Nan Fan, Gui Zhao, Anna Czarna, Zi-Dong Lu, Xiao-Jiao Du, Song Shen, Cong-Fei Xu, Zhe-Xiong Lian, Jun Wang

ACS Applied Materials & Interfaces· Volume 12· Issue 43
Publisher page
Source abstract

Abstract

Nanotechnology has shown great promise in treating diverse diseases. However, developing nanomedicines that can cure autoimmune diseases without causing systemic immunosuppression is still quite challenging. Herein, we propose an all-in-one nanomedicine comprising an autoantigen peptide and CRISPR-Cas9 to restore specific immune tolerance by engineering dendritic cells (DCs) into a tolerogenic phenotype, which can expand autoantigen-specific regulatory T (Treg) cells. In brief, we utilized cationic lipid-assisted poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PEG-PLGA) nanoparticles to simultaneously encapsulate an autoimmune diabetes-relevant peptide (2.5mi), a CRISPR-Cas9 plasmid (pCas9), and three guide RNAs (gRNAs) targeting costimulatory molecules (CD80, CD86, and CD40). We demonstrated that the all-in-one nanomedicine was able to effectively codeliver these components into DCs, followed by simultaneous disruption of the three costimulatory molecules and presentation of the 2.5mi peptide on the genome-edited DCs. The resulting tolerogenic DCs triggered the generation and expansion of autoantigen-specific Treg cells by presenting the 2.5mi peptide to CD4+ T cells in the absence of costimulatory signals. Using autoimmune type 1 diabetes (T1D) as a typical disease model, we demonstrated that our nanomedicine prevented autoimmunity to islet components and inhibited T1D development. Our all-in-one nanomedicine achieved codelivery of CRISPR-Cas9 and the peptide to DCs and could be easily applied to other autoimmune diseases by substitution of different autoantigen peptides.
Source: openalex_inverted_index · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Immune Cell Function and Interaction · CAR-T cell therapy research · T-cell and B-cell Immunology

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

Affiliations

Guangzhou First People’s Hospital, School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 510006, P. R. China

School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, P. R. China

Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei 230027, P. R. China

Institutes for Life Sciences, School of Medicine, South China University of Technology, Guangzhou 510006, P. R. China

Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou 510006, P. R. China

National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, P. R. China

Key Laboratory of Biomedical Engineering of Guangdong Province, and Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, P. R. China

Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510005, P. R. China

Research Institute for Food Nutrition and Human Health, Guangzhou 510641, P. R. China

Funding

Guangdong Science and Technology Department · Guangdong Province Introduction of Innovative R&D Team · State Administration of Foreign Experts Affairs · Ministry of Education of the People's Republic of China · Ministry of Science and Technology of the People's Republic of China · China Postdoctoral Science Foundation · Guangzhou Science and Technology Program key projects · National Natural Science Foundation of China · Natural Science Foundation of Guangdong Province · Guangzhou Regenerative Medicine and Health Guangdong Laboratory

References (42)

Show source-provided references
1. 10.1111/joim.1239510.1111/joim.12395 ↗
2. 10.1172/jci7808810.1172/jci78088 ↗
3. 10.1016/j.immuni.2010.04.00310.1016/j.immuni.2010.04.003 ↗
4. 10.1038/nrdp.2017.1610.1038/nrdp.2017.16 ↗
5. 10.1038/nature0893310.1038/nature08933 ↗
6. 10.1038/nrd340210.1038/nrd3402 ↗
7. 10.1038/nrendo.2014.210.1038/nrendo.2014.2 ↗
8. 10.1056/nejm19880908319100210.1056/nejm198809083191002 ↗
9. 10.2337/db13-034510.2337/db13-0345 ↗
10. 10.1056/nejmoa04398010.1056/nejmoa043980 ↗
11. 10.1016/j.coph.2018.05.01010.1016/j.coph.2018.05.010 ↗
12. 10.1056/nejmoa090445210.1056/nejmoa0904452 ↗
13. 10.1111/j.0105-2896.2006.00427.x10.1111/j.0105-2896.2006.00427.x ↗
14. 10.1016/j.jaut.2016.03.01110.1016/j.jaut.2016.03.011 ↗
15. 10.1126/scitranslmed.aad413410.1126/scitranslmed.aad4134 ↗
16. 10.1016/j.imlet.2013.12.01810.1016/j.imlet.2013.12.018 ↗
17. 10.1038/nrrheum.2016.3310.1038/nrrheum.2016.33 ↗
18. 10.1038/s41587-019-0015-410.1038/s41587-019-0015-4 ↗
19. 10.1073/pnas.140868611110.1073/pnas.1408686111 ↗
20. 10.2337/db07-050710.2337/db07-0507 ↗
21. 10.1016/j.immuni.2010.03.01510.1016/j.immuni.2010.03.015 ↗
22. 10.1038/nature1696210.1038/nature16962 ↗
23. 10.1038/nnano.2017.5610.1038/nnano.2017.56 ↗
24. 10.1002/adma.20190769210.1002/adma.201907692 ↗
25. 10.1016/b978-0-12-380995-7.00004-510.1016/b978-0-12-380995-7.00004-5 ↗
26. 10.1111/j.1600-065x.2011.01015.x10.1111/j.1600-065x.2011.01015.x ↗
27. 10.3389/fphar.2018.0064210.3389/fphar.2018.00642 ↗
28. 10.1038/nprot.2013.14310.1038/nprot.2013.143 ↗
29. 10.1126/science.123114310.1126/science.1231143 ↗
30. 10.1021/acs.chemrev.6b0079910.1021/acs.chemrev.6b00799 ↗
31. 10.1016/j.addr.2019.11.00510.1016/j.addr.2019.11.005 ↗
32. 10.1038/s41565-019-0539-210.1038/s41565-019-0539-2 ↗
33. 10.1089/hum.2015.06710.1089/hum.2015.067 ↗
34. 10.1038/nm.417010.1038/nm.4170 ↗
35. 10.1038/gt.2017.3510.1038/gt.2017.35 ↗
36. 10.1016/j.biomaterials.2019.11930210.1016/j.biomaterials.2019.119302 ↗
37. 10.1038/s41467-018-06522-510.1038/s41467-018-06522-5 ↗
38. 10.1016/j.jconrel.2011.07.03510.1016/j.jconrel.2011.07.035 ↗
39. 10.1016/j.biomaterials.2016.02.03110.1016/j.biomaterials.2016.02.031 ↗
40. 10.1021/acsnano.7b0787410.1021/acsnano.7b07874 ↗
41. 10.1016/j.biomaterials.2018.04.05210.1016/j.biomaterials.2018.04.052 ↗
42. 10.1021/acsnano.9b0144410.1021/acsnano.9b01444 ↗