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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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RNA Interference01:23

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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.
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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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Nucleic Acid Structure01:25

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The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms  a 5′ to 3′ phosphodiester linkage.
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The basic structure of RNA consists of a string of ribonucleotides attached by phosphodiester bonds. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
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Porous Silicon Microparticles for Delivery of siRNA Therapeutics
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Hairpin-like siRNA-Based Spherical Nucleic Acids.

Matthew K Vasher1,2, Gokay Yamankurt2,3, Chad A Mirkin1,2,4

  • 1Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States.

Journal of the American Chemical Society
|February 10, 2022
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Summary

New hairpin-like small interfering RNA-spherical nucleic acid (siRNA-SNA) constructs overcome delivery challenges. This novel design enhances siRNA stability, reduces toxicity, and improves gene knockdown efficiency for therapeutic applications.

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Area of Science:

  • Biotechnology
  • Nanotechnology
  • Molecular Biology

Background:

  • Therapeutic application of small interfering RNAs (siRNAs) is hindered by poor stability and delivery.
  • Spherical nucleic acid (SNA) architectures improve siRNA stability and cellular uptake.
  • Existing hybridized siRNA-SNA designs suffer from guide strand dissociation, limiting active siRNA duplex delivery.

Purpose of the Study:

  • To introduce and investigate a novel hairpin-like SNA architecture for enhanced siRNA delivery.
  • To overcome guide strand dissociation issues inherent in previous siRNA-SNA designs.
  • To improve the stability, delivery efficiency, and gene silencing capabilities of siRNA-based therapeutics.

Main Methods:

  • Design and synthesis of a hairpin-like molecule to immobilize both siRNA strands onto an SNA core.
  • Characterization of the hairpin-like siRNA-SNA construct's loading capacity, stability, and cytotoxicity.
  • In vitro evaluation of gene knockdown efficiency and durability compared to hybridized siRNA-SNAs.

Main Results:

  • The hairpin-like architecture increased siRNA duplex loading capacity by 4-fold compared to hybridized siRNA-SNAs.
  • Hairpin-like siRNA-SNAs demonstrated a 6-fold longer half-life in serum and reduced cytotoxicity.
  • Enhanced and more durable gene knockdown was achieved with the hairpin-like siRNA-SNA construct.

Conclusions:

  • Immobilization chemistry significantly enhances the biological function of siRNA-based nanoparticles.
  • The hairpin-like architecture represents a next-generation SNA construct for improved therapeutic siRNA delivery.
  • This novel design holds promise for advancing life science and medical research applications of gene regulation technologies.