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Protein transfection via spherical nucleic acids.

Sasha B Ebrahimi1,2, Devleena Samanta2,3, Caroline D Kusmierz2,3

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Protein nanoparticles (ProSNAs) enable efficient cellular delivery of proteins, overcoming uptake and degradation issues. This platform offers enhanced stability, activity, and pharmacokinetics for diverse biological applications.

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Area of Science:

  • Nanotechnology
  • Molecular Biology
  • Biochemistry

Background:

  • Efficient intracellular delivery of functional proteins is crucial for biological and medical applications.
  • Current methods are limited by low cellular uptake and protein degradation.
  • Spherical nucleic acids (SNAs) are nanoparticles with nucleic acid shells that actively enter cells.

Purpose of the Study:

  • To develop protein-based nanoparticles (ProSNAs) for enhanced cellular protein delivery.
  • To demonstrate the stability, activity, and pharmacokinetic advantages of ProSNAs.
  • To present ProSNAs as a versatile platform for various biological applications.

Main Methods:

  • Synthesis of ProSNAs via chemical modification of protein cores.
  • Characterization of ProSNAs' structure, stability, and cellular uptake.
  • Evaluation of ProSNAs' activity and pharmacokinetics in vitro and in vivo.

Main Results:

  • ProSNAs facilitate active cellular entry of previously impermeable proteins.
  • ProSNAs exhibit high stability and sustained activity in cellular and in vivo environments.
  • ProSNAs demonstrate enhanced pharmacokinetic profiles compared to free proteins.

Conclusions:

  • ProSNAs represent a modular and "plug-and-play" platform for protein delivery.
  • This technology overcomes key limitations of protein-based therapeutics and diagnostics.
  • ProSNAs offer significant potential for cellular transfection, sensing, and in vivo enzyme delivery.