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Related Concept Videos

siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

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Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
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Porous Silicon Microparticles for Delivery of siRNA Therapeutics
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A design approach for layer-by-layer surface-mediated siRNA delivery.

Jonathan J Chou1, Adam G Berger2, Sasan Jalili-Firoozinezhad3

  • 1Institute for Soldier Nanotechnologies, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.

Acta Biomaterialia
|September 4, 2021
PubMed
Summary

Optimizing layer-by-layer assembly conditions enhances short interfering RNA (siRNA) delivery from coatings. This study reveals how parameters like pH and concentration impact siRNA efficacy for therapeutic applications.

Keywords:
DeliveryDesign of experimentLayer-by-layerPBAEsiRNA

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Molecular Biology

Background:

  • Short interfering RNA (siRNA) therapeutics offer targeted gene silencing for various diseases.
  • Effective delivery systems are crucial for clinical siRNA utility.
  • Layer-by-layer (LbL) technology facilitates siRNA formulation in polyelectrolyte thin films for localized delivery.

Purpose of the Study:

  • To investigate the impact of LbL assembly parameters on siRNA-eluting film composition.
  • To determine how these parameters influence in vitro siRNA-mediated gene knockdown efficiency.
  • To develop optimized conditions for effective and efficient siRNA surface delivery.

Main Methods:

  • Utilized a fractional factorial design to vary LbL assembly parameters (pH, ionic strength, polymer/siRNA concentration).
  • Assembled poly(β-amino ester) (PBAE) and siRNA films on polyglactin 910 sutures.
  • Quantified PBAE and siRNA loading, weight ratios, and assessed in vitro gene knockdown.

Main Results:

  • Identified key LbL assembly parameters affecting film composition and siRNA loading.
  • Demonstrated that optimized conditions yielded significant in vitro gene knockdown (47%).
  • Developed a rationally designed formulation achieving high knockdown with fewer layers, reducing complexity and cost.

Conclusions:

  • LbL solution conditions critically influence the performance of surface-mediated siRNA delivery systems.
  • The study presents an adaptable methodology for optimizing siRNA delivery via LbL coatings.
  • Findings pave the way for improved siRNA therapeutics and delivery of other nucleic acids.