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A decreasing function describes a relationship where the output consistently declines as the input increases. This means that for any two input values, if one is greater than the other, the corresponding output is smaller. Mathematically, a function f is decreasing on an interval I if for every x1 < x2​ in I, f (x1) > f (x2). This type of behavior is visually identified on a graph that slopes downward from left to right.The nature of a function can be analyzed by calculating...
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Peptide-derived Method to Transport Genes and Proteins Across Cellular and Organellar Barriers in Plants
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Development of an indolicidin-derived peptide by reducing membrane perturbation to decrease cytotoxicity and maintain

Ching-Wei Tsai1, Ze-Wei Lin1, Wen-Fang Chang1

  • 1Department of Chemical and Materials Engineering, National Central University, No. 300, Jhongda Rd., Jhongli District, Taoyuan City, 32001, Taiwan.

Colloids and Surfaces. B, Biointerfaces
|February 16, 2018
PubMed
Summary

A new peptide, SAP10, enhances gene delivery by reducing cytotoxicity associated with indolicidin. This safe and efficient peptide promotes polyethylenimine-mediated gene delivery with improved biocompatibility and transfection efficiency.

Keywords:
Cell penetrating peptides (CPPs)CytotoxicityGene deliveryIndolicidinMembrane perturbationMolecular dynamics (MD) simulation

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Biotechnology

Background:

  • Indolicidin (IL) is a cationic antimicrobial peptide with potential as a cell-penetrating peptide (CPP) for gene delivery.
  • However, IL's cytotoxicity due to membrane perturbation limits its clinical use.
  • A novel derivative, SAP10, was designed to improve safety and efficiency.

Purpose of the Study:

  • To design and evaluate SAP10, a novel indolicidin derivative, for enhanced gene delivery.
  • To investigate the interaction of SAP10 with lipid bilayers and its effect on gene delivery complexes.
  • To assess the safety and efficiency of SAP10 in promoting polyethylenimine (PEI)-mediated gene delivery.

Main Methods:

  • All-atom molecular dynamics (MD) simulations were used to study SAP10-lipid bilayer interactions.
  • Ternary nanocomplexes of SAP10, PEI, and DNA were formed for gene delivery.
  • In vitro transfection assays were performed on various cell types to evaluate efficiency and cytotoxicity.

Main Results:

  • SAP10 exhibited reduced lipid bilayer perturbation compared to IL due to its high positive charge density, enhancing biocompatibility.
  • SAP10-associated ternary nanocomplexes significantly improved gene transfection efficiency across various cell types with low cytotoxicity.
  • The beneficial effects of SAP10 on gene delivery were primarily attributed to adsorbed peptides on nanoparticles.

Conclusions:

  • The designed SAP10 peptide is a safe and effective agent for promoting PEI-mediated gene delivery.
  • SAP10 offers improved biocompatibility and enhanced transfection efficiency, broadening its potential clinical applications.
  • Optimization of SAP10 dosage can further enhance its safety profile for gene delivery applications.