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Protein Complexes with Interchangeable Parts01:57

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Polytene chromosomes are giant interphase chromosomes with several DNA strands placed side by side. They were discovered in the year 1881 by Balbiani in salivary glands, intestine, muscles, malpighian tubules, and hypoderm of larvae Chironomus plumosus. Hence, these are also called "Salivary gland chromosomes." These are found in insects of the order Diptera and Collembola; in certain organs of mammals; and synergids, antipodes of flowering plants. Polytene chromosomes are also...
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Quo vadis polyplex?

Olivia M Merkel1, Thomas Kissel2

  • 1Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48201, USA; Department of Oncology, Wayne State University, Detroit, MI 48201, USA.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|June 17, 2014
PubMed
Summary
This summary is machine-generated.

Polymeric siRNA delivery faces slow clinical translation due to limited understanding of carrier biodistribution and excretion. Addressing these knowledge gaps is crucial for developing safe RNA interference (RNAi) therapeutics.

Keywords:
BiodegradationBiodistributionNanocarrierPolymerStabilitysiRNA

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Area of Science:

  • Biomedical Engineering
  • Drug Delivery
  • Nanotechnology

Background:

  • Polymeric siRNA delivery is a key research area for the Journal of Controlled Release, with over 1600 publications.
  • Despite extensive research, clinical translation of polymeric siRNA delivery systems remains slow.

Purpose of the Study:

  • This review critically examines the challenges hindering clinical translation of polymeric siRNA delivery.
  • It focuses on the importance of in vivo studies, carrier biocompatibility, intracellular trafficking, endosomal escape, and serum stability.
  • The review addresses the critical question of polymer biodistribution and excretion for safe repeated administration.

Main Methods:

  • Literature review focusing on in vivo studies and polymeric carrier behavior.
  • Analysis of factors affecting siRNA delivery efficacy and safety.
  • Discussion of knowledge gaps in polymer biodistribution and excretion.

Main Results:

  • Biocompatibility, intracellular entrapment, endosomal release, and serum stability are significant hurdles.
  • There is a substantial lack of data regarding the in vivo biodistribution and excretion of polymeric carriers.
  • This knowledge gap directly impacts the safety and efficacy of repeated administration of RNAi therapeutics.

Conclusions:

  • Closing the knowledge gap on polymer biodistribution and excretion is essential for advancing polymeric siRNA delivery.
  • Further in vivo investigations are critical to ensure the safety and successful clinical translation of RNAi therapeutics.
  • Understanding the fate of polymeric carriers within cells and the body is paramount for developing next-generation therapeutics.