Owen S. Fenton’s research while affiliated with University of North Carolina at Chapel Hill and other places

... 81,84 Using PEGgrafted PEI and amine-containing terminal group PEI modifications, efficient transfection of pulmonary immune cells can be achieved by increasing the PNP stability and reducing the toxicity of PEI. 9 PEI can also be functionalized with alkynoate tails, creating amino acrylate polymers that can be tuned for the delivery of mRNA in normoxic and hypoxic conditions through varying the PEG lipid molecular weight. 91 Interestingly, by including adenosine triphosphate in their formulation, the authors observed higher mRNA expression in hypoxic conditions indicating the need to adjust formulations for hypoxic disease states. ...

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Non-viral mRNA delivery to the lungs

... The cGAS-STING signaling pathway, comprised of cyclic GMP-AMP synthase (cGAS) and the transmembrane protein STING, inserted in the endoplasmic reticulum membrane, plus downstream signaling adapters, plays a crucial role in protective immune defense against microbial infections or internal damage-associated DNA ( Figure 3A). 22,23,28,29 cGAMP effectively activates the STING pathway and its downstream signaling cascades, including TBK1-IRF3 and NF-κB, leading to the induction of type I IFNs, such as IFN-β, and pro-inflammatory cytokines like IFN-γ, thereby enhancing immune responses within the tumor microenvironment. 22,23,28,29 There is significant therapeutic interest in the use of STING agonists for cancer immunotherapy, with nanoparticles presenting a promising approach, 15,16,23,30,31 This includes the role of nanoparticles, capable of overcoming the negative charge of dinucleotides that prevent membrane permeation, as well as protecting the cargo to allow liver uptake. ...

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Reprogramming the Tolerogenic Immune Response Against Pancreatic Cancer Metastases by Lipid Nanoparticles Delivering a STING Agonist Plus Mutant KRAS mRNA

... The palladium-catalyzed substitution reaction of allylic electrophiles has found numerous applications in synthetic organic chemistry [1][2][3] . Since the late 1980s, a number of polymerization methods leveraging this reactivity have been developed by Saegusa, Okada, Endo, Nomura, Leibfarth, and others, affording unsaturated carbon-chain and heterochain polymers via either a step-or chain-growth mechanism ( Fig. 1a) [4][5][6][7][8][9][10][11] . ...

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Controlled chain-growth polymerization via propargyl/allenyl palladium intermediates

... The endosomal escape ability of mRNA-MPN NPs is likely attributed to the buffering capacity imparted by MPNs. Although incorporating polyphenols into NPs can facilitate the endosomal escape of mRNA 39,40 (Supplementary Fig. 18), metal-phenolic coordination exerts synergistic buffering effects, enabling superior endosomal escape capability via enhanced protonsponge effects 41,42 (Supplementary Figs. 17 and 18). ...

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mRNA delivery enabled by metal–organic nanoparticles

... Following the rapid development of both RNA therapeutics and lipid nanoparticles (LNPs), recent reviews have addressed various aspects of this multidisciplinary field, such as organ-specificity [44], non-liver targeting LNPs [45], spleen-targeted LNPs [46], mRNA-LNPs design [47,48], and clinical trials of siRNA therapeutics [49], etc. This review aims to serve as a one-stop shop by holistically examining the history and advancements in liposomal RNA delivery systems. ...

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Enhancing RNA-lipid nanoparticle delivery: Organ- and cell-specificity and barcoding strategies

... It converts medical images into three-dimensional models, providing support for surgical planning and simulation. Lerner and his team have used 3D printing technology to simulate the reconstruction of the flap [17], which makes both high-fidelity and cost-effective facial models available to students, thereby making it easier for students to understand the surgical technique [18]. Moreover, the application of virtual reality technology has created highly realistic surgical simulation environments for students, providing abundant practical opportunities. ...

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Application and exploration of interprofessional education in the teaching of plastic and reconstructive surgery: a narrative review

... RNA therapeutics can ameliorate ADassociated transcriptional and translational changes in microglia. To increase siRNA protection and BBB permeability, William et al. utilized lipid nanoparticles to deliver PU.1 siRNAs (Ralvenius et al., 2024). Local intrathecal injection of liposomal nanoparticles enhances mRNA delivery within the mouse brain, achieving up to 92% ± 2% PU.1 transcriptional silencing within 12 h in mice. ...

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Engineered nanoparticles for the treatment of Alzheimer’s disease

... Decreased bioavailability leads to minimal protein production and low therapeutic efficacy. To overcome the innefficient delivery of the mRNA several molecular designes were implied and a comprehensive descrisption of them was published by Neill, et al., in 2024 [31]. Exogenous mRNA is immunogenic and although it activates the immune system it also increases mRNA degradation and antigen expression [32]. ...

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Antibodies Against Melanoma Antigens -Clinical and Therapeutical Markers

... New LNP components integrating TLR7/8 agonist activity enhance the immunogenicity and delivery efficiency of SARS-CoV-2 mRNA vaccines [150]. Adding ATP to LNP significantly improves mRNA expression and enhances delivery efficiency [151]. All-trans retinoic acid (ATRA) [152] integration in LNPs activates DCs in lymph nodes, promoting T cell response and tumor immunity. ...

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Recent Advancements in mRNA Vaccines: From Target Selection to Delivery Systems

... Using interfering RNA (iRNA) and messenger RNA (mRNA) allows for precise gene modulation, enabling tailored treatment strategies, including precise gene suppression, customized disease treatments, and personalized drug response prediction within personalized medicine [48][49][50][51]. mRNA technology within personalized medicine enables custom protein production, personalized cancer immunotherapy using mRNA-based vaccines, and rapid development of viral vector vaccines, such as those for COVID-19 [52][53][54]. Personalized nanomedicine offers efficient and targeted delivery of immunostimulatory agents for antitumor immune responses, with growing applications in cancer immunology as technology becomes more accessible worldwide. Nanoparticles encapsulated anticancer drugs selectively accumulate in tumor tissues and can attach targeting moieties onto their surface, aiding in immuno-oncology applications. ...

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Scaling nanopharmaceutical production for personalized medicine: challenges and strategies