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Related Concept Videos

RNA Interference01:23

RNA Interference

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RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
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siRNA - Small Interfering RNAs02:30

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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.
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Experimental RNAi02:15

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RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
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Solvent-driven, self-assembled acid-responsive poly(ketalized serine)/siRNA complexes for RNA interference.

Shirley Wong1, Jessica A Kemp, Min Suk Shim

  • 1Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University of California, Irvine, CA 92697, USA. kwonyj@uci.edu.

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Researchers developed novel acid-responsive polypeptide nanoparticles for efficient small interfering RNA (siRNA) delivery. These smart carriers overcome common challenges in gene therapy, improving intracellular targeting and cargo release.

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Area of Science:

  • Bionanotechnology
  • Polymer Chemistry
  • Gene Delivery

Background:

  • Current nucleic acid delivery systems face challenges like poor biodegradability, rapid clearance, and immune responses.
  • Peptide-based nanomaterials offer versatility and biomimetic properties for gene and drug delivery.
  • Acid-labile polypeptide gene vectors are promising for endosomal escape but face synthesis limitations.

Purpose of the Study:

  • To synthesize and polymerize acid-labile peptides under conditions preserving their functional groups.
  • To develop a novel formulation strategy for creating stable, stimuli-responsive nucleic acid delivery complexes.
  • To evaluate the efficiency of these complexes in nucleic acid encapsulation, cellular uptake, and intracellular release.

Main Methods:

  • Synthesized stable urethane derivatives of ketalized serine (kSer) and polymerized them to high molecular weight.
  • Developed a solvent-driven self-assembly method for poly(kSer) peptides and small interfering RNA (siRNA).
  • Cross-linked the self-assembled poly(kSer)/siRNA complexes for enhanced stability under physiological conditions.

Main Results:

  • Achieved high molecular weight polymerization of acid-labile kSer peptides under permissive conditions.
  • Created highly monodisperse, spherical poly(kSer)/siRNA complexes with excellent stability.
  • Demonstrated efficient nucleic acid encapsulation, cellular internalization, endosomal escape, and acid-triggered release.

Conclusions:

  • Acid-responsive polypeptides and solvent-driven self-assembly offer a promising strategy for developing safe and efficient gene delivery systems.
  • The developed poly(kSer)/siRNA complexes effectively address multiple hurdles in siRNA delivery.
  • This approach has broad applicability for creating advanced delivery systems for nucleic acids and drugs.