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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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Bacterial Delivery of RNAi Effectors: Transkingdom RNAi
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A modular platform for targeted RNAi therapeutics.

Ranit Kedmi1, Nuphar Veiga1, Srinivas Ramishetti1

  • 1Laboratory of Precision NanoMedicine, School of Molecular Cell Biology and Biotechnology, George S. Wise Faculty of Life Sciences, Department of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Center for Nanoscience and Nanotechnology, Cancer Biology Research Center, Tel Aviv University, Tel Aviv, Israel.

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|January 31, 2018
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Summary
This summary is machine-generated.

This study introduces a novel modular platform for creating targeted short interfering RNA (siRNA) delivery systems. This breakthrough facilitates precision medicine by enabling customizable targeting of therapeutic nucleic acids to specific cells.

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Area of Science:

  • Biotechnology and Nanomedicine
  • Gene Therapy and Drug Delivery

Background:

  • Gene expression modulation using short interfering RNAs (siRNAs) holds promise for personalized medicine.
  • Current siRNA delivery systems, often relying on chemical conjugation with monoclonal antibodies (mAbs), face challenges in clinical translation due to production complexity and batch variability.

Discussion:

  • A novel self-assembled modular platform for siRNA delivery carriers is presented, overcoming limitations of current technologies.
  • The platform utilizes membrane-anchored lipoproteins integrated into siRNA-loaded lipid nanoparticles that interact with the antibody crystallizable fragment (Fc) domain.
  • Switching eight different monoclonal antibodies (mAbs) effectively redirects siRNA uptake by various leukocyte subsets in vivo.

Key Insights:

  • Demonstrated therapeutic efficacy in an inflammatory bowel disease model by targeting colon macrophages to reduce inflammation.
  • Showcased potential in a Mantle Cell Lymphoma xenograft model by targeting cancer cells, inducing cell death and improving survival.
  • The platform enables the construction of a theoretically unlimited repertoire of siRNA targeted carriers.

Outlook:

  • This self-assembled modular delivery platform represents a significant advancement in precision medicine.
  • The technology offers a versatile and scalable approach for developing targeted nucleic acid therapeutics.
  • Potential applications span various diseases requiring targeted gene modulation therapies.