دورية أكاديمية
An AAV capsid reprogrammed to bind human transferrin receptor mediates brain-wide gene delivery.
| العنوان: | An AAV capsid reprogrammed to bind human transferrin receptor mediates brain-wide gene delivery. |
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| المؤلفون: | Huang Q; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Chan KY; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Wu J; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Botticello-Romero NR; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Zheng Q; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Lou S; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Keyes C; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Svanbergsson A; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Johnston J; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Mills A; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Lin CY; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Brauer PP; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Clouse G; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Pacouret S; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Harvey JW; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Beddow T; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Hurley JK; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Tobey IG; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Powell M; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Chen AT; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Barry AJ; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Eid FE; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA.; Department of Systems and Computer Engineering, Faculty of Engineering, Al-Azhar University, Cairo 11651, Egypt., Chan YA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA., Deverman BE; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA. |
| المصدر: | Science (New York, N.Y.) [Science] 2024 Jun 14; Vol. 384 (6701), pp. 1220-1227. Date of Electronic Publication: 2024 May 16. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Original Publication: New York, N.Y. : [s.n.] 1880- |
| مواضيع طبية MeSH: | Antigens, CD*/metabolism , Antigens, CD*/genetics , Brain*/metabolism , Capsid*/metabolism , Gene Transfer Techniques* , Genetic Vectors* , Receptors, Transferrin*/metabolism , Receptors, Transferrin*/genetics , Glucosylceramidase*/genetics, Animals ; Humans ; Mice ; Blood-Brain Barrier/metabolism ; Capsid Proteins/metabolism ; Capsid Proteins/genetics ; Dependovirus ; Endothelial Cells/metabolism ; Gene Knock-In Techniques ; Genetic Therapy ; Gaucher Disease/genetics ; Gaucher Disease/therapy ; Parkinson Disease/genetics ; Parkinson Disease/therapy |
| مستخلص: | Developing vehicles that efficiently deliver genes throughout the human central nervous system (CNS) will broaden the range of treatable genetic diseases. We engineered an adeno-associated virus (AAV) capsid, BI-hTFR1, that binds human transferrin receptor (TfR1), a protein expressed on the blood-brain barrier. BI-hTFR1 was actively transported across human brain endothelial cells and, relative to AAV9, provided 40 to 50 times greater reporter expression in the CNS of human TFRC knockin mice. The enhanced tropism was CNS-specific and absent in wild-type mice. When used to deliver GBA1 , mutations of which cause Gaucher disease and are linked to Parkinson's disease, BI-hTFR1 substantially increased brain and cerebrospinal fluid glucocerebrosidase activity compared with AAV9. These findings establish BI-hTFR1 as a potential vector for human CNS gene therapy. |
| التعليقات: | Update of: bioRxiv. 2023 Dec 22:2023.12.20.572615. doi: 10.1101/2023.12.20.572615. (PMID: 38187643) |
| المشرفين على المادة: | 0 (Antigens, CD) 0 (Capsid Proteins) 0 (CD71 antigen) 0 (Receptors, Transferrin) EC 3.2.1.45 (GBA protein, human) EC 3.2.1.45 (Glucosylceramidase) |
| تواريخ الأحداث: | Date Created: 20240516 Date Completed: 20240613 Latest Revision: 20240621 |
| رمز التحديث: | 20240622 |
| DOI: | 10.1126/science.adm8386 |
| PMID: | 38753766 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1095-9203 |
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| DOI: | 10.1126/science.adm8386 |