Nuclear-Targeting Delivery of CRISPRa System for Upregulation of β-Defensin against Virus Infection by Dexamethasone and Phenylalanine Dual-Modified Dendrimer
The dual-modified dendrimer containing dexamethasone (DET) and phenylalanine (Phe) was prepared to deliver plasmid DNA encoding dCas9 and single-guide RNA (sgRNA) for specific upregulation of β-defensin. DET and Phe moieties synergistically enhanced the transfection efficiency and reduced cytotoxici...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-01-01
|
| Series: | Advances in Polymer Technology |
| Online Access: | http://dx.doi.org/10.1155/2020/6582825 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832566327374512128 |
|---|---|
| author | Mingxiang Zuo Xiaoxia Li Shuang Liu Bin Chen Du Cheng |
| author_facet | Mingxiang Zuo Xiaoxia Li Shuang Liu Bin Chen Du Cheng |
| author_sort | Mingxiang Zuo |
| collection | DOAJ |
| description | The dual-modified dendrimer containing dexamethasone (DET) and phenylalanine (Phe) was prepared to deliver plasmid DNA encoding dCas9 and single-guide RNA (sgRNA) for specific upregulation of β-defensin. DET and Phe moieties synergistically enhanced the transfection efficiency and reduced cytotoxicity of dendrimers. Combination of three sgRNAs targeting β-defensin gene demonstrated higher activation efficacy of β-defensin than any single sgRNA and combinations of any two sgRNAs, showing an efficient inhibition of virus infection and replication. The titer of vesicular stomatitis virus (VSV) in the cells treated with dCas9-sgRNA targeting β-defensin was reduced by about 100-fold compared to that of cells treated with dCas9-scramble sgRNA (dCas9-scr sgRNA). In vivo experiments demonstrated that the DET- and Phe-modified dendrimer effectively delivered plasmid DNA encoding dCas9 protein into the airway epithelium, inducing β-defensin expression. Delivery of the CRISPR activation system by a dendrimer modified with DET and Phe was a promising approach against viral disease. |
| format | Article |
| id | doaj-art-293648893ebc4461b8d6250871f5f9cf |
| institution | Kabale University |
| issn | 0730-6679 1098-2329 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advances in Polymer Technology |
| spelling | doaj-art-293648893ebc4461b8d6250871f5f9cf2025-02-03T01:04:19ZengWileyAdvances in Polymer Technology0730-66791098-23292020-01-01202010.1155/2020/65828256582825Nuclear-Targeting Delivery of CRISPRa System for Upregulation of β-Defensin against Virus Infection by Dexamethasone and Phenylalanine Dual-Modified DendrimerMingxiang Zuo0Xiaoxia Li1Shuang Liu2Bin Chen3Du Cheng4PCFM Lab of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, ChinaPCFM Lab of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, ChinaZhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510275, ChinaDepartment of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaPCFM Lab of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, ChinaThe dual-modified dendrimer containing dexamethasone (DET) and phenylalanine (Phe) was prepared to deliver plasmid DNA encoding dCas9 and single-guide RNA (sgRNA) for specific upregulation of β-defensin. DET and Phe moieties synergistically enhanced the transfection efficiency and reduced cytotoxicity of dendrimers. Combination of three sgRNAs targeting β-defensin gene demonstrated higher activation efficacy of β-defensin than any single sgRNA and combinations of any two sgRNAs, showing an efficient inhibition of virus infection and replication. The titer of vesicular stomatitis virus (VSV) in the cells treated with dCas9-sgRNA targeting β-defensin was reduced by about 100-fold compared to that of cells treated with dCas9-scramble sgRNA (dCas9-scr sgRNA). In vivo experiments demonstrated that the DET- and Phe-modified dendrimer effectively delivered plasmid DNA encoding dCas9 protein into the airway epithelium, inducing β-defensin expression. Delivery of the CRISPR activation system by a dendrimer modified with DET and Phe was a promising approach against viral disease.http://dx.doi.org/10.1155/2020/6582825 |
| spellingShingle | Mingxiang Zuo Xiaoxia Li Shuang Liu Bin Chen Du Cheng Nuclear-Targeting Delivery of CRISPRa System for Upregulation of β-Defensin against Virus Infection by Dexamethasone and Phenylalanine Dual-Modified Dendrimer Advances in Polymer Technology |
| title | Nuclear-Targeting Delivery of CRISPRa System for Upregulation of β-Defensin against Virus Infection by Dexamethasone and Phenylalanine Dual-Modified Dendrimer |
| title_full | Nuclear-Targeting Delivery of CRISPRa System for Upregulation of β-Defensin against Virus Infection by Dexamethasone and Phenylalanine Dual-Modified Dendrimer |
| title_fullStr | Nuclear-Targeting Delivery of CRISPRa System for Upregulation of β-Defensin against Virus Infection by Dexamethasone and Phenylalanine Dual-Modified Dendrimer |
| title_full_unstemmed | Nuclear-Targeting Delivery of CRISPRa System for Upregulation of β-Defensin against Virus Infection by Dexamethasone and Phenylalanine Dual-Modified Dendrimer |
| title_short | Nuclear-Targeting Delivery of CRISPRa System for Upregulation of β-Defensin against Virus Infection by Dexamethasone and Phenylalanine Dual-Modified Dendrimer |
| title_sort | nuclear targeting delivery of crispra system for upregulation of β defensin against virus infection by dexamethasone and phenylalanine dual modified dendrimer |
| url | http://dx.doi.org/10.1155/2020/6582825 |
| work_keys_str_mv | AT mingxiangzuo nucleartargetingdeliveryofcrisprasystemforupregulationofbdefensinagainstvirusinfectionbydexamethasoneandphenylalaninedualmodifieddendrimer AT xiaoxiali nucleartargetingdeliveryofcrisprasystemforupregulationofbdefensinagainstvirusinfectionbydexamethasoneandphenylalaninedualmodifieddendrimer AT shuangliu nucleartargetingdeliveryofcrisprasystemforupregulationofbdefensinagainstvirusinfectionbydexamethasoneandphenylalaninedualmodifieddendrimer AT binchen nucleartargetingdeliveryofcrisprasystemforupregulationofbdefensinagainstvirusinfectionbydexamethasoneandphenylalaninedualmodifieddendrimer AT ducheng nucleartargetingdeliveryofcrisprasystemforupregulationofbdefensinagainstvirusinfectionbydexamethasoneandphenylalaninedualmodifieddendrimer |