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Additional Subnuclear Structures

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A perspective on the apparent pKa of ionizable lipids in mRNA-LNPs.

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A perspective on bleb and empty LNP structures.

Jens B Simonsen1

  • 1Jbsimonsen Consult, Grønnevej 160, 2830 Virum, Denmark.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|July 27, 2024
PubMed
Summary
This summary is machine-generated.

Lipid nanoparticles (LNPs) used for mRNA delivery can contain "blebs" and empty particles. This perspective explores their impact on safety and efficacy, proposing methods for their study and quantification to improve LNP drug development.

Keywords:
BlebEmptyLNPLipid nanoparticlesQuantifcationStructures

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Area of Science:

  • Biotechnology
  • Drug Delivery Systems
  • Nanomedicine

Background:

  • Lipid nanoparticles (LNPs) are FDA-approved for mRNA delivery.
  • Understanding LNP heterogeneity is crucial for optimizing their use.
  • Blebs and empty LNPs are common structural and compositional variations.

Purpose of the Study:

  • To discuss the presence and implications of blebs and empty LNPs.
  • To review existing literature on LNP structural heterogeneities.
  • To propose novel strategies for studying and quantifying these features.

Main Methods:

  • Literature review of key articles on LNP structural and compositional heterogeneities.
  • Analysis of conflicting views on the attributes of blebs and empty LNPs.
  • Discussion of current and novel approaches for quantification.

Main Results:

  • Conflicting views exist regarding the impact of blebs and empty LNPs.
  • Limited systematic studies exist on the safety and efficacy implications.
  • Current research and quality control methods for dealing with these heterogeneities are discussed.

Conclusions:

  • Further research is needed to understand the role of blebs and empty LNPs.
  • Novel strategies for studying these features could enhance LNP development.
  • Embracing, leveraging, or mitigating these heterogeneities may improve LNP-based drug products.