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lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA)...

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Exploring the Effects of Incorporating Different Bioactive Phospholipids into Messenger Ribonucleic Acid Lipid

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Researchers explored adding bioactive phospholipids to lipid-nanoparticle (LNP) formulations for RNA therapeutics. This fifth component modulated LNP properties and biological functions, expanding design possibilities for effective drug delivery.

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Area of Science:

  • Biotechnology
  • Nanomedicine
  • Drug Delivery Systems

Background:

  • Advancements in ribonucleic acid (RNA) therapeutics rely heavily on innovative drug delivery systems, particularly lipid-nanoparticle (LNP) based formulations.
  • Conventional LNP formulations comprise four key lipid components, each crucial for stability and efficacy.
  • Phospholipids, while providing structural support, possess bioactive properties with significant cell signaling potential.

Purpose of the Study:

  • To investigate the incorporation of structurally related bioactive phospholipids as a fifth component in conventional LNP formulations.
  • To assess the impact of adding bioactive phospholipids on the physicochemical properties and biological functions of messenger RNA (mRNA) LNP formulations.

Main Methods:

  • Screening a library of mRNA LNP formulations with seven different bioactive phospholipids at 5%, 15%, and 30% molar concentrations.
  • Analyzing physicochemical properties, including structural integrity via Cryo-electron microscopy (Cryo-EM).
  • Evaluating biological functions through protein expression in HeLa cells and cytokine profiling in human peripheral blood mononuclear cells (hPBMCs).

Main Results:

  • Observed variations in physicochemical properties influenced by phospholipid type and concentration.
  • Cryo-EM confirmed structural similarity across different LNP formulations.
  • Distinct cytokine profiles were identified for each formulation in hPBMCs, with CD4+ T cells being the primary transfected cell type, and altered cellular tropism noted.

Conclusions:

  • The addition of bioactive phospholipids can effectively modulate LNP function.
  • This approach expands the design space for RNA LNP formulations.
  • Incorporating bioactive phospholipids offers a strategy to potentiate LNPs for advanced RNA therapeutics.