6FDB

Positively supercharged variant of the computationally designed cage protein O3-33

Summary for 6FDB

• Entry DOI: 10.2210/pdb6fdb/pdb
• Descriptor: Propanediol utilization protein (1 entity in total)
• Functional Keywords: computationally designed cage protein, o3-33, de novo protein
• Biological source: Salmonella choleraesuis
• Total number of polymer chains: 8
• Total formula weight: 161066.98

Authors

Edwardson, T.,Mori, T.,Hilvert, D. (deposition date: 2017-12-22, release date: 2018-08-22, Last modification date: 2024-01-17)

Primary citation

Edwardson, T.G.W.,Mori, T.,Hilvert, D.
Rational Engineering of a Designed Protein Cage for siRNA Delivery.
J. Am. Chem. Soc., 140:10439-10442, 2018

PubMed Abstract: Oligonucleotide therapeutics have transformative potential in modern medicine but are poor drug candidates in themselves unless fitted with compensatory carrier systems. We describe a simple approach to transform a designed porous protein cage into a nucleic acid delivery vehicle. By introducing arginine mutations to the lumenal surface, a positively supercharged capsule is created, which can encapsidate oligonucleotides in vitro with high binding affinity. We demonstrate that the siRNA-loaded cage is taken up by mammalian cells and releases its cargo to induce RNAi and knockdown gene expression. These general concepts could also be applied to alternative scaffold designs, expediting the development of artificial protein cages toward delivery applications.

PubMed: 30091604
DOI: 10.1021/jacs.8b06442

Experimental method

X-RAY DIFFRACTION (3.619 Å)