.png){kind=icon}
.png){kind=icon}
Return
Intracellular Delivery of Peptides and Proteins with an Engineered Membrane Translocation Domain
.png){kind=icon}
OA
AI
P
H
J
B
T
Q
V
L
J
D
DOI：10.1021/acschembio.6c00383.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Antibodies and other protein therapeutics have revolutionized medicine, but their application is largely limited to extracellular targets. The lack of efficient intracellular delivery methods remains a major bottleneck. Here, we engineered a family of small (∼90 amino acids), metabolically stable membrane translocation domains (MTDs) by modifying the loop sequences of a human fibronectin type III (FN3) domain. The most potent variant, MTD4, is highly cell-permeable and can be recombinantly fused to the N- or C-terminus of any peptide or protein, serving as a versatile delivery vehicle. We demonstrate that MTD4 fusions efficiently deliver a wide variety of functional peptides and proteins into the cytosol and nucleus of eukaryotic cells, both in vitro and in vivo. Following systemic administration, an MTD4 fusion protein exhibited broad biodistribution and homogeneous tissue penetration in mice. Importantly, MTD4 is effective at low nanomolar (nM) concentrations, making it a promising platform for addressing a vast range of intracellular and previously ″undruggable″ targets.
Keywords:
Cells
Drug delivery
Fluorescence
Peptides and proteins
Rodent models
Journal
IF:
3.8
Papers:
5.4K
Citations:
1.7W
Organization
Cited Papers