Graphical Abstract[出典] REVIEW "Advances in the design and delivery of RNA vaccines for infectious diseases" Lokras AG, Bobak TR, Baghel SS, Sebastiani F, Foged C. Adv Drug Deliv Rev 2024-08-05. https://doi.org/10.1016/j.addr.2024.115419 [所属] U Copenhagen, Lund U；参考図 [グラフィカルアブストラクト引用右図]；参考文献399件を含む33頁

　RNA医薬品は、世界的に重要な疾患、例えば感染症の治療と予防におけるパラダイムシフトを象徴している。大成功を収めた新型コロナウイルス（SARS-CoV-2）に対するメッセンジャーRNA（mRNA）ワクチンは、COVID-19の大流行時に記録的なスピードで開発された。この結果、ワクチン開発期間が例外的に短縮され、適応性と相まって、RNAワクチン技術は感染症やパンデミック対策にとって魅力的なものとなった。

　Fig. 1ここでは、直鎖状mRNA、自己増幅型RNA （saRNA）、トランス増幅型RNA（taRNA）、環状RNAなど、さまざまなRNA様式に基づく感染症用RNAワクチンの設計と送達に関する最新技術を概説する [Fig. 1引用右図参照]。また、感染症用RNAワクチンの臨床パイプラインの概要を提供し、品質属性の特徴づけと品質保証のために最も重要な分析手順を提示し、SARS-CoV-2以外の病原体と闘うためにRNAワクチンを使用するための将来の展望について議論する。

[構成]
1. Introduction
1.1. Infectious diseases and the need for vaccines
1.2. mRNA as a tool to hijack the flow of information of life
1.3. Conventional non-replicating linear mRNA vaccines
1.4. Vaccines based on self-amplifying RNA (saRNA)
1.5. Vaccines based on trans-amplifying RNA
1.6. Vaccines based on circular RNA
2. Delivery systems for RNA vaccines
2.1. Lipid-based RNA delivery systems
2.2. Polymer-based RNA delivery systems
2.3. Hybrid systems
2.4. Other RNA delivery strategies
3. Clinical status
3.1. Approved RNA vaccines
3.2. Vaccines based on RNA in the pipeline
4. Vaccines based on RNA against infectious diseases in preclinical development
4.1. RNA vaccines against viral diseases
4.2. RNA vaccines against bacterial diseases
4.3. RNA vaccines against fungal diseases
4.4. RNA vaccines against protozoal diseases
5. Manufacturing and quality control
5.1. Manufacturing
5.2. Characterization and quality control − mRNA substance
5.3. Characterization and quality control − mRNA vaccine
5.4. Advanced methods to characterize nanoparticles
6. Thermostability of RNA-LNPs
7. Conclusions and perspectives

[図表一覧]
  • Fig. 1. Different RNA modalities and their mechanism of antigen expression
  • Fig. 2. The molecular shape hypothesis.
  • Fig. 3. Rational development of new generation aminolipids.
  • Fig. 4. Examples of polymer-based systems investigated for RNA vaccine delivery.
  • Fig. 6Fig. 5. Delivery system loaded with: (i) mRNA encoding a single antigen (left), and (ii) mRNA encoding a protein assembling in situ into virus-like particle (VLP) proteins combined with antigen in a polycistronic construct (right).
  • Fig. 6. Mechanism of action of RNA-based vaccines [右図に引用]
  • Fig. 7. Composition of approved COVID-19 mRNA vaccines
  • Table 1. Examples of polymer-based systems investigated for RNA delivery.
  • Table 2. Approved vaccines based on RNA.
  • Table 3. RNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in clinical trials.
  • Table 4. Examples of RNA vaccines against influenza in clinical trials.
  • Table 5. RNA vaccines against combined targets in clinical trials.
  • Table 6. Examples of RNA vaccines against various targets in clinical trials.
  • Table 7. Analytical methods used for characterization and release testing of mRNA substance.
  • Table 8. Analytical methods used for characterization and release testing of mRNA vaccine.