Effect of Cholesterol Content of Lipid Composition in mRNA-LNPs on the Protein Expression in the Injected Site and Liver After Local Administration in Mice

Kawaguchi, Maho; Noda, Marin; Ono, Akari; Kamiya, Mariko; Matsumoto, Makoto; Tsurumaru, Masako; Mizukami, Shusaku; Mukai, Hidefumi; Kawakami, Shigeru

doi:10.1016/j.xphs.2022.12.026

Cited by 26 publications

(7 citation statements)

References 36 publications

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“…This suggests that ionizable lipids play a crucial role in both antigen generation and innate immune signaling, although the precise mechanism responsible for immune activation remains incompletely understood. The PEGylated lipids in the formulation protect the nanoparticle from opsonization and phagocytosis, allowing for prolonged circulation 56,57 . Lastly the helper lipids, cholesterol and DSPC, enhance the stability of the nanoparticle by stabilizing the antigen encapsulation and enhancing membrane rigidity which leads to overall greater efficacy and biodistribution 57–59 .…”

Section: Current Clinical Trialsmentioning

confidence: 99%

“…The PEGylated lipids in the formulation protect the nanoparticle from opsonization and phagocytosis, allowing for prolonged circulation. 56 , 57 Lastly the helper lipids, cholesterol and DSPC, enhance the stability of the nanoparticle by stabilizing the antigen encapsulation and enhancing membrane rigidity which leads to overall greater efficacy and biodistribution. 57 , 58 , 59 Once the host cell is infected, the mRNA is translated into a SARS‐CoV‐2 spike protein that expresses on the host cell.…”

Section: Current Clinical Trialsmentioning

confidence: 99%

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Vaccine adjuvants for infectious disease in the clinic

Goetz,

Thotathil,

Zhao

et al. 2024

Bioengineering & Transla Med

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Adjuvants, materials added to vaccines to enhance the resulting immune response, are important components of vaccination that are many times overlooked. While vaccines always include an antigen to tell the body what to vaccinate to, of equal importance the adjuvant provides the how, a significant factor in producing a complete response. The adjuvant space has been slow to develop with the first use of an adjuvant in a licensed vaccine occurring in the 1930s, and remaining the only adjuvant in licensed vaccines for the next 80 years. However, with vaccination at the forefront of protection against new and complex pathogens, it is important to consider all components when designing an effective vaccine. Here we summarize the adjuvant space in licensed vaccines as well as the novel adjuvant space in clinical trials with a specific focus on the materials utilized and their resulting impact on the immune response. We discuss five major categories of adjuvant materials: aluminum salts, nanoparticles, viral vectors, TLR agonists, and emulsions. For each category, we delve into the current clinical trials space, the impact of these materials on vaccination, as well as some of the ways in which they could be improved. Adjuvants present an exciting opportunity to improve vaccine responses and stability, this review will help inform about the current progress of this space.Translational impact statementIn the aftermath of the COVID‐19 pandemic, vaccines for infectious diseases have come into the spotlight. While antigens have always been an important focus of vaccine design, the adjuvant is a significant tool for enhancing the immune response to the vaccine that has been largely underdeveloped. This article provides a broad review of the history of adjuvants and, the current vaccine adjuvant space, and the progress seen in adjuvants in clinical trials. There is specific emphasis on the material landscape for adjuvants and their resulting mechanism of action. Looking ahead, while the novel vaccine adjuvant space features exciting new technologies and materials, there is still a need for more to meet the protective needs of new and complex pathogens.

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Section: Current Clinical Trialsmentioning

confidence: 99%

Section: Current Clinical Trialsmentioning

confidence: 99%

Vaccine adjuvants for infectious disease in the clinic

Goetz,

Thotathil,

Zhao

et al. 2024

Bioengineering & Transla Med

View full text Add to dashboard Cite

show abstract

“…According to Kawaguchi et al. [ 58 ], the cellular internalization and protein expression decreased both in vitro and in vivo when the molar percentage of CHO was reduced from 40% to 10%. In addition, at a lower CHO content, the size of LNPs increased from 75.4 nm to 140 nm, and encapsulation efficiency decreased to 65%, causing unstable physicochemical properties of LNPs.…”

Section: Lipid and Lnp Formulations For Mrna Medicinesmentioning

confidence: 99%

Unlocking the Therapeutic Applicability of LNP-mRNA: Chemistry, Formulation, and Clinical Strategies

Huang,

Ma,

et al. 2024

Research

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Messenger RNA (mRNA) has emerged as an innovative therapeutic modality, offering promising avenues for the prevention and treatment of a variety of diseases. The tremendous success of mRNA vaccines in effectively combatting coronavirus disease 2019 (COVID-19) evidences the unlimited medical and therapeutic potential of mRNA technology. Overcoming challenges related to mRNA stability, immunogenicity, and precision targeting has been made possible by recent advancements in lipid nanoparticles (LNPs). This review summarizes state-of-the-art LNP-mRNA-based therapeutics, including their structure, material compositions, design guidelines, and screening principles. Additionally, we highlight current preclinical and clinical trends in LNP-mRNA therapeutics in a broad range of treatments in ophthalmological conditions, cancer immunotherapy, gene editing, and rare-disease medicine. Particular attention is given to the translation and evolution of LNP-mRNA vaccines into a broader spectrum of therapeutics. We explore concerns in the aspects of inadequate extrahepatic targeting efficacy, elevated doses, safety concerns, and challenges of large-scale production procedures. This discussion may offer insights and perspectives on near- and long-term clinical development prospects for LNP-mRNA therapeutics.

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“… 56 It is involved in the degradation of LNPs within the systemic circulation and assists in their subcellular transport. 63 , 64 Recently, researchers have begun to focus on optimizing the formulation of LNPs. For example, Patel et al have investigated substituting cholesterol with hydroxycholesterol to enhance mRNA delivery to T cells, thereby promoting the endosomal escape of LNPs and advancing their applications in immunotherapy.…”

Section: Lipid Nanoparticle Delivery Systems: An Overview and Composi...mentioning

confidence: 99%

Research Advances of Lipid Nanoparticles in the Treatment of Colorectal Cancer

Zhang,

Ali,

Wang

2024

IJN

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Effect of Cholesterol Content of Lipid Composition in mRNA-LNPs on the Protein Expression in the Injected Site and Liver After Local Administration in Mice

Cited by 26 publications

References 36 publications

Vaccine adjuvants for infectious disease in the clinic

Vaccine adjuvants for infectious disease in the clinic

Unlocking the Therapeutic Applicability of LNP-mRNA: Chemistry, Formulation, and Clinical Strategies

Research Advances of Lipid Nanoparticles in the Treatment of Colorectal Cancer

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