DEGylation Enhanced the Stability of Peptide-siRNA Complexes in Serum

Ran, Pan; Xu, Wen; Jafari, Mousa; Chen, Baoling; Sheinin, Tatiana; Chen, P

doi:10.1166/jnn.2015.12074

Cited by 4 publications

(2 citation statements)

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“…It has been reported by many studies that blood stability is the major barrier for a cationic polymeric vector-mediated RNA delivery system . Many transfection studies were performed in a medium with no serum or low serum, thus resulting in a significant inconsistency between the in vitro and in vivo transfection studies. , To avoid unnecessary usage of animals, the in vitro transfection study should be conducted under high serum conditions (>10%). To evaluate how the serum content in culture medium affects the delivery of dextran–peptides, 10% and 20% FBS were added in the culture medium and cells were transfected at concentrations of 30 and 100 nM siPCSK9.…”

Section: Resultsmentioning

confidence: 99%

Biomimetic Dextran–Peptide Vectors for Efficient and Safe siRNA Delivery

Wang

et al. 2019

ACS Appl. Bio Mater.

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Small interfering RNA (siRNA)-based therapeutics have the potential to treat a series of hereditary and acquired diseases. However, one serious obstacle for siRNA therapy is the lack of an efficient strategy to transport the siRNA to the targeted organ/cell with minimal toxicity. To take advantage of the good biocompatibility and degradability of natural polymers, and to understand how the peptide sequence affects the properties of the vector, four biomimetic vectors (D10-K3H7, D10-R3H7, D20-K3H7, and D20-R3H7) were designed and synthesized by conjugating the peptide (K3H7 or R3H7) and dextran with a molecular weight of 10 or 20 kDa. Taking the commercial cellular transfection reagent Lipofectime RNAiMAX as a control, dextran–peptide/siRNA complexes exhibited smaller particle sizes, lower ζ potentials, and lower toxicity with the same value of N/P ratio. To evaluate the potential of this system for therapeutics, siRNA targeting the mRNA of the PCSK9 gene was chosen as a gene drug model to knock down the PCSK9 expression in the HepG2 cell line. Dextran–peptide/siRNA complexes exhibit a more consistent and higher knockdown efficiency than Lipofectamine RNAiMAX/PCSK9 siRNA complexes in a medium with 20% fetal bovine serum (FBS). D20-R3H7/PCSK9 siRNA complexes could knock down the level of PCSK9 mRNA by 85.2%, and they demonstrated a higher efficiency than Lipofectamine RNAiMAX, having 70.5% knockdown in the medium with 20% FBS at the PCSK9 siRNA concentration of 100 nM. These results suggest that the dextran–peptide-based vector has more efficient therapeutic agent properties for a siRNA-based drug transporter.

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Section: Resultsmentioning

confidence: 99%

Biomimetic Dextran–Peptide Vectors for Efficient and Safe siRNA Delivery

Wang

et al. 2019

ACS Appl. Bio Mater.

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“…Concerning serum stability and other safety issues, the field of CPEs can certainly profit from the extensive research on those aspects for other protein therapeutics. For example, Pan et al developed a strategy to enhance serum stability of a CPP-RNA conjugate by coupling it to diethylene glycol (DEGylation), 236 similar to the attachment of polyethylene glycol (PEGylation) to conventional protein therapeutics.…”

Section: Resultsmentioning

confidence: 99%

Immunomodulatory Yersinia outer proteins (Yops)–useful tools for bacteria and humans alike

2017

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Human-pathogenic Yersinia produce plasmid-encoded Yersinia outer proteins (Yops), which are necessary to down-regulate anti-bacterial responses that constrict bacterial survival in the host. These Yops are effectively translocated directly from the bacterial into the target cell cytosol by the type III secretion system (T3SS). Cell-penetrating peptides (CPPs) in contrast are characterized by their ability to autonomously cross cell membranes and to transport cargoindependent of additional translocation systems. The recent discovery of bacterial cellpenetrating effector proteins (CPEs) -with the prototype being the T3SS effector protein YopM -established a new class of autonomously translocating immunomodulatory proteins. CPEs represent a vast source of potential self-delivering, anti-inflammatory therapeutics. In this review, we give an update on the characteristic features of the plasmid-encoded Yops and, based on recent findings, propose the further development of these proteins for potential therapeutic applications as natural or artificial cell-penetrating forms of Yops might be of value as bacteria-derived biologics.

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