Synthesis and bioactivity of readily hydrolysable novel cationic lipids for potential lung delivery application of mRNAs

Pei, Yihua; Bao, Yuping; Sacchetti, Cristiano; Brady, Juthamart; Gillard, Kyra; Yu, Hailong; Roberts, Scott; Rajappan, Kumar; Tanis, Steven P.; Pérez-García, Carlos G.; Chivukula, Padmanabh; Karmali, Priya

doi:10.1016/j.chemphyslip.2022.105178

Cited by 16 publications

(7 citation statements)

References 52 publications

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“…In this section, recent progress in the design of cationic and ionizable lipids and their functions relating to mRNA-LNPs formulations is described. mRNA-LNPs mainly consist of four components in addition to mRNA [ 94 ]: (1) cationic or ionizable lipids with positive charges that bind to negatively charged mRNA, (2) PEGylated lipids that coat the LNPs and stabilize mRNA, (3) phospholipids, and (4) cholesterol molecules that maintain structural integrity [ 95 ]. The cationic or ionizable lipids are amphiphilic molecules that typically feature a polar head group, a hydrophobic tail, and a heteroatom linker between the two components [ 96 ] (Fig.…”

Section: Prevention For Covid-19mentioning

confidence: 99%

“…5 C, DODMA was one of the first ionizable lipids for gene delivery. Its single alkyl-chains were originally used in the design of ionizable lipids, but these components slowed the process of biodegradation [ 95 ], making the complex undesirable for clinical administration. To solve this biodegradation issue [ 112 ], redesign of the linker (e.g., ester, disulfide or phosphate bonds) and polar head group (e.g., guanidinium salt) were undertaken, introducing alternative hydrophobic chains or ionizable lipids (Fig.…”

Section: Prevention For Covid-19mentioning

confidence: 99%

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A critical overview of current progress for COVID-19: development of vaccines, antiviral drugs, and therapeutic antibodies

Kumari

et al. 2022

J Biomed Sci

102

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The novel coronavirus disease (COVID-19) pandemic remains a global public health crisis, presenting a broad range of challenges. To help address some of the main problems, the scientific community has designed vaccines, diagnostic tools and therapeutics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The rapid pace of technology development, especially with regard to vaccines, represents a stunning and historic scientific achievement. Nevertheless, many challenges remain to be overcome, such as improving vaccine and drug treatment efficacies for emergent mutant strains of SARS-CoV-2. Outbreaks of more infectious variants continue to diminish the utility of available vaccines and drugs. Thus, the effectiveness of vaccines and drugs against the most current variants is a primary consideration in the continual analyses of clinical data that supports updated regulatory decisions. The first two vaccines granted Emergency Use Authorizations (EUAs), BNT162b2 and mRNA-1273, still show more than 60% protection efficacy against the most widespread current SARS-CoV-2 variant, Omicron. This variant carries more than 30 mutations in the spike protein, which has largely abrogated the neutralizing effects of therapeutic antibodies. Fortunately, some neutralizing antibodies and antiviral COVID-19 drugs treatments have shown continued clinical benefits. In this review, we provide a framework for understanding the ongoing development efforts for different types of vaccines and therapeutics, including small molecule and antibody drugs. The ripple effects of newly emergent variants, including updates to vaccines and drug repurposing efforts, are summarized. In addition, we summarize the clinical trials supporting the development and distribution of vaccines, small molecule drugs, and therapeutic antibodies with broad-spectrum activity against SARS-CoV-2 strains.

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Section: Prevention For Covid-19mentioning

confidence: 99%

Section: Prevention For Covid-19mentioning

confidence: 99%

A critical overview of current progress for COVID-19: development of vaccines, antiviral drugs, and therapeutic antibodies

Kumari

et al. 2022

J Biomed Sci

102

View full text Add to dashboard Cite

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“…The fragmented lipids need to be metabolized in the plasma because these smaller fragments are often carried into systemic circulation. Hence, plasma stability is an applicable measure of overall biodegradability and potential for accumulation over time ( Pei et al, 2022 ).…”

Section: Cleavage Of Lipid Nanoparticlesmentioning

confidence: 99%

Potential of siRNA in COVID-19 therapy: Emphasis on in silico design and nanoparticles based delivery

Fopase

Panda

Rajendran

et al. 2023

Front. Bioeng. Biotechnol.

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Small interfering RNA (siRNA)-mediated mRNA degradation approach have imparted its eminence against several difficult-to-treat genetic disorders and other allied diseases. Viral outbreaks and resulting pandemics have repeatedly threatened public health and questioned human preparedness at the forefront of drug design and biomedical readiness. During the recent pandemic caused by the SARS-CoV-2, mRNA-based vaccination strategies have paved the way for a new era of RNA therapeutics. RNA Interference (RNAi) based approach using small interfering RNA may complement clinical management of the COVID-19. RNA Interference approach will primarily work by restricting the synthesis of the proteins required for viral replication, thereby hampering viral cellular entry and trafficking by targeting host as well as protein factors. Despite promising benefits, the stability of small interfering RNA in the physiological environment is of grave concern as well as site-directed targeted delivery and evasion of the immune system require immediate attention. In this regard, nanotechnology offers viable solutions for these challenges. The review highlights the potential of small interfering RNAs targeted toward specific regions of the viral genome and the features of nanoformulations necessary for the entrapment and delivery of small interfering RNAs. In silico design of small interfering RNA for different variants of SARS-CoV-2 has been discussed. Various nanoparticles as promising carriers of small interfering RNAs along with their salient properties, including surface functionalization, are summarized. This review will help tackle the real-world challenges encountered by the in vivo delivery of small interfering RNAs, ensuring a safe, stable, and readily available drug candidate for efficient management of SARS-CoV-2 in the future.

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“…Therefore, the effect of ionizable lipids on mRNA delivery efficiency depends on the pH at which they are protonated and the ability of ionizable lipids to form non-bilayer structures. The introduction of ionizable lipids enhances the role of mRNA in vivo, and the addition of ionizable lipids not only maintains mRNA delivery efficacy but also achieves rapid metabolism, improves the tolerance of lipid nanoparticles, and enhances the effectiveness of tumor immunotherapy ( Figure 4 ) [ 159 , 160 , 161 , 162 , 163 , 164 , 165 ]. For example, researchers have developed an ionizable lipid material to facilitate mRNA delivery in vivo and to provide an effective immune-activated mRNA delivery vehicle to stimulate a strong immune response and inhibit the growth of tumor volume [ 166 ].…”

Section: Development Of Lipids For Mrna Deliverymentioning

confidence: 99%

Lipid Nanoparticles for mRNA Delivery to Enhance Cancer Immunotherapy

Wang

Liu

2022

Molecules

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Messenger RNA (mRNA) is being developed by researchers as a novel drug for the treatment or prevention of many diseases. However, to enable mRNA to fully exploit its effects in vivo, researchers need to develop safer and more effective mRNA delivery systems that improve mRNA stability and enhance the ability of cells to take up and release mRNA. To date, lipid nanoparticles are promising nanodrug carriers for tumor therapy, which can significantly improve the immunotherapeutic effects of conventional drugs by modulating mRNA delivery, and have attracted widespread interest in the biomedical field. This review focuses on the delivery of mRNA by lipid nanoparticles for cancer treatment. We summarize some common tumor immunotherapy and mRNA delivery strategies, describe the clinical advantages of lipid nanoparticles for mRNA delivery, and provide an outlook on the current challenges and future developments of this technology.

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Synthesis and bioactivity of readily hydrolysable novel cationic lipids for potential lung delivery application of mRNAs

Cited by 16 publications

References 52 publications

A critical overview of current progress for COVID-19: development of vaccines, antiviral drugs, and therapeutic antibodies

A critical overview of current progress for COVID-19: development of vaccines, antiviral drugs, and therapeutic antibodies

Potential of siRNA in COVID-19 therapy: Emphasis on in silico design and nanoparticles based delivery

Lipid Nanoparticles for mRNA Delivery to Enhance Cancer Immunotherapy

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