Targeting transgenic proteins to alpha granules for platelet-directed gene therapy.
alpha granular targeting
bone marrow transplantation model
lentiviral vectors
platelet-directed gene therapy
platelet alpha granules
sorting signals
Journal
Molecular therapy. Nucleic acids
ISSN: 2162-2531
Titre abrégé: Mol Ther Nucleic Acids
Pays: United States
ID NLM: 101581621
Informations de publication
Date de publication:
08 Mar 2022
08 Mar 2022
Historique:
received:
14
07
2021
accepted:
30
12
2021
entrez:
4
2
2022
pubmed:
5
2
2022
medline:
5
2
2022
Statut:
epublish
Résumé
Platelets are anucleate blood cells that are shed from megakaryocytes (MKs) into the bloodstream to maintain hemostasis and promote wound healing after vascular injury. To carry out their functions, platelets become activated and release bioactive substances from their secretory granules. As alpha granules (αGs) in resting platelets store proteins and release them only after activation, the packaging of proteins into αGs is an attractive strategy to deliver therapeutic proteins. Here, we propose an adjustable model for targeting transgenic proteins to platelet αGs using third-generation self-inactivating lentiviral vectors. The vectors express from the murine platelet factor 4 promoter (mPf4P), restricting transgene expression to the MK lineage. For the delivery and retention of expressed proteins in αGs, proteins are fused to short peptide sorting signals derived from the human cytokine RANTES or from the transmembrane protein P-selectin. We demonstrate effective targeting of GFP to αGs of murine and human
Identifiants
pubmed: 35116189
doi: 10.1016/j.omtn.2021.12.038
pii: S2162-2531(22)00003-8
pmc: PMC8783114
doi:
Types de publication
Journal Article
Langues
eng
Pagination
774-786Informations de copyright
© 2022 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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