Cell Penetrating Peptide PEG Derivatives

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JenKem Technology introduces a novel patented product line of LMWP Cell Penetrating Peptides – PEG derivatives capable to transport siRNA efficiently through the cell membrane and release siRNA into the cytoplasm. These products, developed in collaboration with Tianjin Medical University, are useful for intracellular delivery of RNA and DNA oligonucleotide and other molecules that cannot penetrate the cell membrane.

Introducing therapeutic genetic material into cells is key for gene therapy. Naked siRNA has poor stability and is easily degraded by the nuclease in vivo, and its properties such as high negative charge, and hydrophilicity prevent its transport through the cell membrane. Cell Penetrating Peptides (CPPs), also called transduction peptides, are short peptides that can carry macromolecules into cells. Although CPPs can deliver different types of substances into cells, their practical application has focused on the cellular transport of oligopeptides, proteins, and nucleic acids. The disadvantage of using CPPs is that a large number of cationic penetrating peptides may cause side effects due to non-specific interactions with negatively charged molecules in cells or negatively charged extracellular molecules into cells. Moreover, the electrostatic interaction between siRNA and transmembrane peptides is a disadvantage for siRNA-based nucleic acid drug delivery.Novel Cell Penetrating PEG Drug Delivery System for siRNA_ JenKem Technology

Introducing a polyethylene glycol flexible segment between CPP and the nucleic acid prevents avoids the electrostatic interaction between the nucleic acid drug and the membrane-penetrating peptide which causes aggregation and sedimentation. This in turn allows the nucleic acid drug to exert its biological activity in the cytoplasm and enhance its bioavailability after entering the cell. The molecular weight of polyethylene glycol can be adjusted according to the specific type of nucleic acid drug delivered, the specific type of transmembrane peptide and the difference of the charge between the two.

In vitro findings confirmed that CPP-PEG drug delivery system yields successful cellular uptake of siRNA and ensures a high gene-silencing efficacy for siRNA.


Application for intracellular delivery of molecules that cannot penetrate the cell membrane, such as oligonucleotides / genes

In vitro demonstrated cellular uptake of siRNA and high gene-silencing efficacy of delivered siRNA

Cleavable linkage for cytosolic release of delivered molecules

Common aggregation and sedimentation problems for oligos are reduced or eliminated by the PEG segment

The CPP-PEG conjugates have low toxicity, are not tissue specific and will not cause any disruption to the cell membrane

CPP-PEGs provided with a variety of activated groups on the PEG, such as but no limited to OPSS, Maleimide, Thiol, or Biotin; as well as conjugates of CPPs-PEG with RNA / DNA and other molecules. Contact us for more details.


1. Zhao, X., et al., Novel Cell-Penetrating Drug Delivery System for siRNA, 2018 TIDES, Poster presentation.