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Related Concept Videos

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.
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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Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...
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Delivery of Therapeutic siRNA to the CNS Using Cationic and Anionic Liposomes
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Multifunctional pH-Sensitive Amino Lipids for siRNA Delivery.

Maneesh Gujrati1, Amita Vaidya1, Zheng-Rong Lu1

  • 1Department of Biomedical Engineering, Case Western Reserve University , Cleveland, Ohio 44106, United States.

Bioconjugate Chemistry
|December 3, 2015
PubMed
Summary

Multifunctional pH-sensitive lipids enable efficient delivery of small interfering RNA (siRNA) for gene silencing. These advanced lipid nanoparticles facilitate targeted delivery and endosomal escape, showing promise for treating aggressive cancers.

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Area of Science:

  • Biotechnology
  • Nanomedicine
  • Molecular Biology

Background:

  • RNA interference (RNAi) therapy uses small interfering RNA (siRNA) to regulate gene expression.
  • Efficient siRNA delivery to the cytoplasm is crucial for RNAi efficacy but remains a major challenge.
  • Lipid-based siRNA delivery systems offer advantages in formulation and nanoparticle creation.

Purpose of the Study:

  • To review recent advancements in pH-sensitive amino lipids for siRNA delivery.
  • To highlight multifunctional pH-sensitive lipids and their components for enhanced siRNA delivery.
  • To discuss the application of these lipids in targeted cancer therapy.

Main Methods:

  • Focus on multifunctional pH-sensitive amino lipids with specific structural features (protonatable head group, lipid tails, thiol groups).
  • Discuss nanoparticle formation, surface modification for targeting, endosomal escape mechanisms, and reductive dissociation for siRNA release.
  • Review structure-property relationships and in vitro/in vivo efficacy of these lipids.

Main Results:

  • Multifunctional pH-sensitive lipids facilitate stable siRNA-nanoparticle formation and targeted delivery.
  • These lipids enable efficient endosomal escape and cytoplasmic release of siRNA.
  • Targeted siRNA nanoparticles effectively regulated cancer-related genes in aggressive tumors, including metastatic triple-negative breast cancer.

Conclusions:

  • Multifunctional pH-sensitive lipids are a promising platform for systemic and targeted siRNA delivery.
  • These lipids can mediate efficient gene silencing and demonstrate significant therapeutic efficacy in preclinical cancer models.
  • Further development of these lipid systems holds potential for treating various human diseases via RNAi.