Functional Delivery of siRNA by Disulfide-Constrained Cyclic Amphipathic Peptides.
The promise of oligonucleotide therapeutic agents to perturb expression of disease-related genes remains unrealized, in part due to challenges with functional cellular delivery of these agents. Herein, we describe disulfide-constrained cyclic amphipathic peptides that complex with short-interfering RNA (siRNA) and affect functional cytosolic delivery and knockdown of target gene products in cell culture and in vivo to mouse lung. Reduction of the constraining disulfide bond and subsequent proteolytic clearance of the peptide are key design features that allow unmasking of the siRNA cargo and presentation to the RNA interference machinery.
Department of Chemistry, University of Rochester , Rochester, New York 14627, United States.
Jade J
JJ
Welch
Department of Chemistry, University of Rochester , Rochester, New York 14627, United States.
Ria J
RJ
Swanekamp
Department of Pediatrics and Neonatology, University of Rochester Medical Center, School of Medicine and Dentistry, University of Rochester , Rochester, New York 14642, United States.
Christiaan
C
King
Department of Pediatrics and Neonatology, University of Rochester Medical Center, School of Medicine and Dentistry, University of Rochester , Rochester, New York 14642, United States.
David A
DA
Dean
Department of Chemistry, University of Rochester , Rochester, New York 14627, United States.
Bradley L
BL
Nilsson
cell-penetrating peptides; cyclic peptides; siRNA delivery