Lipid Nanoparticle-Mediated Delivery of mRNA Therapeutics and Vaccines

Swingle, Kelsey L.; Hamilton, Alex G.; Mitchell, Michael J.

doi:10.1016/j.molmed.2021.03.003

Cited by 74 publications

(66 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The design of simple, effective, and cost-efficient processes to assess the required purity of EVs will facilitate much-needed standardization in the field. Careful consideration and standardized/regulatory requirements for challenges raised in this and other key reviews ( Willis et al, 2018 ; Whitford and Guterstam, 2019 ; Wiklander et al, 2019 ; Gandham et al, 2020 ; Nguyen et al, 2020 ; Rankin-Turner et al, 2021 ) will assist in development of EV-based therapeutics, bringing them closer to the clinic ( Davis et al, 2008 ; Chan et al, 2010 ; Buss and Bhatia, 2020 ; Li et al, 2021c ; Swingle et al, 2021 ; Yang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Development of Extracellular Vesicle Therapeutics: Challenges, Considerations, and Opportunities

Claridge

Lozano

Poh

et al. 2021

Front. Cell Dev. Biol.

111

View full text Add to dashboard Cite

Extracellular vesicles (EVs) hold great promise as therapeutic modalities due to their endogenous characteristics, however, further bioengineering refinement is required to address clinical and commercial limitations. Clinical applications of EV-based therapeutics are being trialed in immunomodulation, tissue regeneration and recovery, and as delivery vectors for combination therapies. Native/biological EVs possess diverse endogenous properties that offer stability and facilitate crossing of biological barriers for delivery of molecular cargo to cells, acting as a form of intercellular communication to regulate function and phenotype. Moreover, EVs are important components of paracrine signaling in stem/progenitor cell-based therapies, are employed as standalone therapies, and can be used as a drug delivery system. Despite remarkable utility of native/biological EVs, they can be improved using bio/engineering approaches to further therapeutic potential. EVs can be engineered to harbor specific pharmaceutical content, enhance their stability, and modify surface epitopes for improved tropism and targeting to cells and tissues in vivo. Limitations currently challenging the full realization of their therapeutic utility include scalability and standardization of generation, molecular characterization for design and regulation, therapeutic potency assessment, and targeted delivery. The fields’ utilization of advanced technologies (imaging, quantitative analyses, multi-omics, labeling/live-cell reporters), and utility of biocompatible natural sources for producing EVs (plants, bacteria, milk) will play an important role in overcoming these limitations. Advancements in EV engineering methodologies and design will facilitate the development of EV-based therapeutics, revolutionizing the current pharmaceutical landscape.

show abstract

Section: Discussionmentioning

confidence: 99%

Development of Extracellular Vesicle Therapeutics: Challenges, Considerations, and Opportunities

Claridge

Lozano

Poh

et al. 2021

Front. Cell Dev. Biol.

111

View full text Add to dashboard Cite

show abstract

“…Encapsulation within lipid nanoparticles has proven successful in recent years for first-in-kind RNA-based therapies, notably the siRNA therapeutic patsiran (Onpattro) approved by the FDA in 2018 for the treatment of hereditary amyloidogenic transthyretin amyloidosis [ 128 ] and the novel class of mRNA-based SARS-CoV-2 vaccines developed for the COVID-19 pandemic [ 129 ]. These lipid nanoparticles typically comprise an ionizable cationic lipid thought to interact with negatively charged bilayer lipids to destabilize endocytic organelle membranes, and three helper lipids (cholesterol, a PEGylated lipid and a structural lipid such as distearoylphosphatidylcholine) that improve stability and augment endocytic organelle escape [ 130 ]. Mechanistic understanding of the latter process may well enable more successful development of new delivery systems [ 127 ].…”

Section: Applications Of Endocytic Organelle Disruption In Medicinementioning

confidence: 99%

Maintenance and loss of endocytic organelle integrity: mechanisms and implications for antigen cross-presentation

et al. 2021

View full text Add to dashboard Cite

The membranes of endosomes, phagosomes and macropinosomes can become damaged by the physical properties of internalized cargo, by active pathogenic invasion or by cellular processes, including endocytic maturation. Loss of membrane integrity is often deleterious and is, therefore, prevented by mitigation and repair mechanisms. However, it can occasionally be beneficial and actively induced by cells. Here, we summarize the mechanisms by which cells, in particular phagocytes, try to prevent membrane damage and how, when this fails, they repair or destroy damaged endocytic organelles. We also detail how one type of phagocyte, the dendritic cell, can deliberately trigger localized damage to endocytic organelles to allow for major histocompatibility complex class I presentation of exogenous antigens and initiation of CD8 + T-cell responses to viruses and tumours. Our review highlights mechanisms for the regulation of endocytic organelle membrane integrity at the intersection of cell biology and immunology that could be co-opted for improving vaccination and intracellular drug delivery.

show abstract

“…Some of the vaccine formulations for COVID-19 that are currently used are nanotechnology-based. The mRNA in the Pfizer/BioNTech and Moderna vaccines are delivered in lipid nanoparticle formulations [ 6 , 8 , 10 ]. In this context, nanotechnology refers to the engineering of particles, which are in the nanoscale (1–1000 nm) and serve as systems to deliver a nucleic acid payload into cellular and subcellular sites in the body.…”

Section: Nanotechnology and Vaccines For Covid-19mentioning

confidence: 99%

“…An unprecedented effort to develop vaccines to prevent COVID-19 infections and make them clinically available for mass immunizations globally started immediately once the causative organism was identified and its molecular signatures were elucidated in early 2020 [ 6 , 7 ]. The advanced drug delivery systems of nanoparticles have been applied to deliver nucleic acid-based vaccines to cellular and subcellular sites [ 8 ]. The research and development efforts for vaccines have been led, as they have traditionally been, largely by countries in the global north [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

A Perspective on Nanotechnology and COVID-19 Vaccine Research and Production in South Africa

Dube

Egieyeh

Balogun

2021

Viruses

View full text Add to dashboard Cite

Advances in nanotechnology have enabled the development of a new generation of vaccines, which are playing a critical role in the global control of the COVID-19 pandemic and the return to normalcy. Vaccine development has been conducted, by and large, by countries in the global north. South Africa, as a major emerging economy, has made extensive investments in nanotechnology and bioinformatics and has the expertise and resources in vaccine development and manufacturing. This has been built at a national level through decades of investment. In this perspective article, we provide a synopsis of the investments made in nanotechnology and highlight how these could support innovation, research, and development for vaccines for this disease. We also discuss the application of bioinformatics tools to support rapid and cost-effective vaccine development and make recommendations for future research and development in this area to support future health challenges.

show abstract

Lipid Nanoparticle-Mediated Delivery of mRNA Therapeutics and Vaccines

Cited by 74 publications

References 10 publications

Development of Extracellular Vesicle Therapeutics: Challenges, Considerations, and Opportunities

Development of Extracellular Vesicle Therapeutics: Challenges, Considerations, and Opportunities

Maintenance and loss of endocytic organelle integrity: mechanisms and implications for antigen cross-presentation

A Perspective on Nanotechnology and COVID-19 Vaccine Research and Production in South Africa

Contact Info

Product

Resources

About