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Updated: May 8, 2026

Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting

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Differential endosomal pathways for radically modified peptide vectors.

Piret Arukuusk¹, Ly Pärnaste, Helerin Margus

¹Laboratory of Molecular Biotechnology, Institute of Technology, University of Tartu , Nooruse 1, 50411 Tartu, Estonia.

Bioconjugate Chemistry

|August 29, 2013

Summary

This summary is machine-generated.

Two NickFect peptides, NF51 and NF1, effectively deliver plasmid DNA (pDNA) into cells via distinct cellular uptake pathways. Despite structural differences, both achieve high gene delivery efficacy, mediated by SCARA receptors.

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Area of Science:

Biotechnology
Molecular Biology
Cell Biology

Background:

Plasmid DNA (pDNA) delivery is crucial for gene therapy and research.
NickFect peptides are novel vectors for pDNA condensation and delivery.
Understanding uptake mechanisms is key to optimizing gene delivery systems.

Purpose of the Study:

To characterize the cellular uptake mechanisms of NickFect peptides NF51 and NF1.
To investigate the role of SCARA receptors in pDNA delivery mediated by NF51 and NF1.
To correlate structural modifications of peptides with their gene delivery pathways and efficacy.

Main Methods:

Condensation of pDNA into nanoparticles with NF51 and NF1.
Transfection of HeLa cells and efficacy assessment.
Analysis of cellular uptake pathways using endocytosis inhibitors and receptor identification (SCARA3, SCARA5).
Investigation of endosomal trafficking and lysosomotropic properties.

Main Results:

Both NF51 and NF1 condense pDNA into nanoparticles with high transfection efficacy.
pDNA delivery is mediated by SCARA3 and SCARA5 receptors for both vectors.
NF51/pDNA enters cells via macropinocytosis; NF1/pDNA uses clathrin/caveolae-mediated endocytosis and macropinocytosis.
NF51 exhibits lysosomotropic properties, enhancing endosomal escape.
NF1 forms less homogeneous and stable nanoparticles compared to NF51.

Conclusions:

Structural modifications in NickFect peptides (e.g., kinks, charge) yield high gene delivery efficacy.
Differential uptake pathways (macropinocytosis vs. clathrin/caveolae-mediated endocytosis) are employed by NF51 and NF1.
SCARA receptors are essential mediators for pDNA delivery by both NF51 and NF1.
Understanding these distinct mechanisms can inform the design of improved gene delivery vectors.