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Direct Protein Delivery to Mammalian Cells Using Cell-permeable Cys2-His2 Zinc-finger Domains

Direct Protein Delivery to Mammalian Cells Using Cell-permeable Cys2-His2 Zinc-finger Domains

Published on: March 25, 2015

Cell-Specific Delivery Using an Engineered Protein Nanocage.

Mikail D Levasseur¹, Shiksha Mantri¹, Takahiro Hayashi¹

¹Laboratory of Organic Chemistry, ETH Zurich, 8093 Zurich, Switzerland.

ACS Chemical Biology

|April 21, 2021

Summary

This summary is machine-generated.

Protein nanocages offer potential for targeted drug delivery and bioimaging. However, while antibody binding enhances cell uptake, it can also attract interfering antibodies, limiting therapeutic efficacy.

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Engineering Cell-permeable Protein

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Published on: December 28, 2009

Area of Science:

Biotechnology
Nanomedicine
Protein Engineering

Background:

Nanoparticle delivery systems show promise for theranostics and bioimaging.
Protein-based nanocages can be engineered for biomacromolecular cargo encapsulation.

Purpose of the Study:

To evaluate a protein nanocage system for targeted delivery of encapsulated cargo.
To investigate the impact of antibody-binding domains on nanocage immunogenicity and targeting efficacy.

Main Methods:

Engineered a cage-forming variant of lumazine synthase to encapsulate cargo.
Linked antibody-binding domains to the nanocage exterior for targeted cell uptake.
Assessed nanocage immunogenicity and the effect of serum antibodies on targeting.

Main Results:

Antibody-binding domains facilitated cell-specific uptake of encapsulated cargo.
Protein nanocages showed reduced immunogenicity compared to unmodified versions.
Recruitment of serum antibodies by the nanocages partially masked targeting antibody efficacy.

Conclusions:

Protein-based nanocages are a viable platform for targeted delivery applications.
The presence of serum antibodies presents a challenge for antibody-mediated targeting strategies.
Further optimization is needed to overcome limitations for practical nanoparticle-based delivery.