Lipid Nanoparticle Technologies for Nucleic Acid Delivery: A Nanoarchitectonics Perspective

Ferhan, Abdul Rahim; Park, Soo-Hyun; Park, Hyeonjin; Tae, Hyunhyuk; Jackman, Joshua A.; Cho, Nam‐Joon

doi:10.1002/adfm.202203669

Cited by 59 publications

(39 citation statements)

References 358 publications

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“…Furthermore, there are many other underexplored lipid-membrane-targeting compounds ranging from interfacially active peptides including various host defense peptides, 38 antimicrobial peptoids, 69 and analogs of the AH peptide 70 to photosensitizers 71 and H 2 S donors 66 that potentially act against enveloped viruses in a more potent and selective way. In addition, there are numerous possibilities for exploiting model membranes to improve the delivery efficacy of lipid-based gene delivery systems based on biophysical characterizations 72 and nanoarchitecture design strategies, 73 which can be done by adapting and extending the existing frameworks built on membrane interface research.…”

Section: Discussionmentioning

confidence: 99%

Lipid Membrane Interface Viewpoint: From Viral Entry to Antiviral and Vaccine Development

Park

Cho

2022

Langmuir

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Membrane-enveloped viruses are responsible for most viral pandemics in history, and more effort is needed to advance broadly applicable countermeasures to mitigate the impact of future outbreaks. In this Perspective, we discuss how biosensing techniques associated with lipid model membrane platforms are contributing to improving our mechanistic knowledge of membrane fusion and destabilization that is closely linked to viral entry as well as vaccine and antiviral drug development. A key benefit of these platforms is the simplicity of interpreting the results which can be complemented by other techniques to decipher more complicated biological observations and evaluate the biophysical functionalities that can be correlated to biological activities. Then, we introduce exciting application examples of membrane-targeting antivirals that have been refined over time and will continue to improve based on biophysical insights. Two ways to abrogate the function of viral membranes are introduced here: (1) selective disruption of the viral membrane structure and (2) alteration of the membrane component. While both methods are suitable for broadly useful antivirals, the latter also has the potential to produce an inactivated vaccine. Collectively, we emphasize how biosensing tools based on membrane interfacial science can provide valuable information that could be translated into biomedicines and improve their selectivity and performance.

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Section: Discussionmentioning

confidence: 99%

Lipid Membrane Interface Viewpoint: From Viral Entry to Antiviral and Vaccine Development

Park

Cho

2022

Langmuir

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“…As a delivery vehicle, LNP benefits from the inclusion of various excipients since each one serves a distinct purpose. 57 Hirai, Y. et al 49 established an approach to producing Lipid nanoparticles (LNPs) based on the pH-sensitive, charge-reversible lipid dioleoylglycerophosphate-diethylenediamine (DOP-DEDA), which achieved effective protein transport into cells. In order to prevent adverse effects caused by the interaction of the lipid with cationic lipids (e.g., cytotoxicity, including the lung surfactant effect), it was engineered to have a negative charge in the extracellular environment with neutral pH.…”

Section: Strategy Of Non-covalent Modification For Intracellular Prot...mentioning

confidence: 99%

Receptor-Targeted Dual pH-Triggered Intracellular Protein Transfer

Lyu

Yazdi

Lin

et al. 2022

ACS Biomater. Sci. Eng.

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Protein therapeutics, including monoclonal antibodies, cytokines, transcription factors, enzymes, and peptides, play an essential role against cancer, infectious diseases, cardiovascular disorders, immunological diseases, and metabolic disorders, resulting in brilliant successes. [9][10][11] Compared with chemotherapy, the critical function of protein therapeutics in treating diseases that lack effective therapeutic options relies on the unique advantages of (i) abundant species; (ii) complex set of biological functions; (iii) high specificity; (iv) fewer adverse effects; (v) excellent biocompatibility and biodegradability; and (vi) inherent amino, carboxyl, and hydroxyl groups for chemical conjugations. 12 Proteins, in contrast to genetic drugs, act on their targets in a way that is both more direct and more specific. This allows them to regulate biological processes in a way that eliminates the risk of permanent gene mutation, off-target effects brought on by persistent gene expression, and the possibility of cancer development. 11 Major challenges of protein therapeuticsThe progress path toward clinical application of proteins is neither straightforward nor uncomplicated, for example, due to the limited administration routes, low bioavailability of proteins in circulation, and host immune responses that may result in the inactivation of proteins before reaching their sites of action. 13 Therefore, biotechnologists have employed tremendous efforts to overcome the delivery drawbacks 2, 14, 15 to protect them from denaturation and degradation, facilitate tumor-targeted delivery, and control the protein release/activity in targeted sites. 16,17 Most protein medicines now available on the market were created based on extracellular targets. These extracellular targets include cell membrane proteins (PD1, HER2, CD20, etc.) and secretory proteins (TNFα, IL12, VEGF, etc.). 11,18 Despite the success of current protein products that mostly address extracellular targets, efficient cytosolic delivery of Ju, E. et al. 36 first reported that gold nanoclusters (AuNCs) can self-assemble with Streptococcus pyogenes Cas9 (SpCas9) protein under physiological conditions, and the complexes (SpCas9-AuNCs) efficiently deliver SpCas9 protein into the cell nucleus.SpCas9-AuNCs could be disassembled at a lower pH 4.5 but are stable at a higher pH 7.4. SpCas9 is delivered into cells and the cell nucleus, where it performs its cleavage function, through the assembly disassembly process. Furthermore, the E6 oncogene was effectively knockout by self-assembled SpCas9-AuNCs nanoparticles after the HPV18 E6 sgRNA transfected into cervical cancer cells. Consequently, this causes the tumorsuppressing protein p53 to resume its normal activity and induces apoptosis in cervical cancer cells but had little effect on the normal cells. Because of their unique characteristics, SpCas9-AuNCs are an intriguing biomaterial for the treatment of cancer.Nanogels are water-rich nanoscale three-dimensional polymer networks. Because of this, it is simple for nan...

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“…1,14,18 If mixing is slow or incomplete during the LNP formation step, then this may result in a larger nanoparticle size, broader particle size distribution, and decreased nucleic acid encapsulation. 18,19 Consequently, the rate and manner of mixing are critical to the formation of uniform LNPs with controlled physicochemical properties and structure. The presence of residual ethanol and changes in the pH, ionic content, and osmolality of the surrounding environment can further modulate LNP physicochemical properties and structure.…”

Section: Introductionmentioning

confidence: 99%

Process Robustness in Lipid Nanoparticle Production: A Comparison of Microfluidic and Turbulent Jet Mixing

O’Brien Laramy,

Costa,

Cebrero

et al. 2023

Mol. Pharmaceutics

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The recent clinical and commercial success of lipid nanoparticles (LNPs) for nucleic acid delivery has incentivized the development of new technologies to manufacture LNPs. As new technologies emerge, researchers must determine which technologies to assess and how to perform comparative evaluations. In this article, we use a quality-by-design approach to systematically investigate how the mixer technology used to form LNPs influences LNPstructure. Specifically, a coaxial turbulent jet mixer and a staggered herringbone microfluidic mixer were systematically compared via matched formulation and process conditions. A full-factorial design-of-experiments study with three factors and three levels was executed for each mixer to compare process robustness in the production of antisense oligonucleotide (ASO) LNPs. ASO-LNPs generated with the coaxial turbulent jet mixer were consistently smaller, had a narrower particle size distribution, and had a higher ASO encapsulation as compared to the microfluidic mixer, but had a greater variation in internal structure with less ordered cores. A subset of the study was replicated for mRNA-LNPs with comparable trends in particle size and encapsulation, but more frequent bleb features for LNPs produced by the coaxial turbulent jet mixer. The study design used here provides a road map for how researchers may compare different mixer technologies (or process changes more broadly) and how such studies can inform process robustness and manufacturing control strategies.

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Lipid Nanoparticle Technologies for Nucleic Acid Delivery: A Nanoarchitectonics Perspective

Cited by 59 publications

References 358 publications

Lipid Membrane Interface Viewpoint: From Viral Entry to Antiviral and Vaccine Development

Lipid Membrane Interface Viewpoint: From Viral Entry to Antiviral and Vaccine Development

Receptor-Targeted Dual pH-Triggered Intracellular Protein Transfer

Process Robustness in Lipid Nanoparticle Production: A Comparison of Microfluidic and Turbulent Jet Mixing

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