Article
Chemistry, Multidisciplinary
Annabelle Biscans, Socheata Ly, Nicholas McHugh, David A. Cooper, Anastasia Khvorova
Summary: The study demonstrates the importance of lipid conjugation in improving siRNA endosomal escape and tissue distribution. Modulating the nature of the conjugate can affect the intratissue distribution and non-specific gene modulation of siRNA.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Chemistry, Multidisciplinary
Marine Z. C. Hatit, Curtis N. Dobrowolski, Melissa P. Lokugamage, David Loughrey, Huanzhen Ni, Chiara Zurla, Alejandro Da Silva J. Sanchez, Afsane Radmand, Sebastian G. Huayamares, Ryan Zenhausern, Kalina Paunovska, Hannah E. Peck, Jinwhan Kim, Manaka Sato, Jacob I. Feldman, Michael-Alexander Rivera, Ana Cristian, YongTae Kim, Philip J. Santangelo, James E. Dahlman
Summary: Stereochemistry affects the pharmacokinetics, safety, and efficacy of small molecules. It is unclear whether the stereochemistry of a single compound within a multicomponent colloid can influence its activity in vivo.
Article
Chemistry, Multidisciplinary
Taewon Jeon, David C. Luther, Ritabrita Goswami, Charlotte Bell, Harini Nagaraj, Yagiz Anil Cicek, Rui Huang, Javier A. Mas-Rosario, James L. Elia, Jungkyun Im, Yi-Wei Lee, Yuanchang Liu, Federica Scaletti, Michelle E. Farkas, Jesse Mager, Vincent M. Rotello
Summary: Polyplexes of siRNA and an engineered cationic polymer (PONI-Guan) can efficiently regulate pro-inflammatory gene expression in pulmonary tissue, showing anti-inflammatory activity in vitro and in vivo.
Article
Chemistry, Multidisciplinary
Alejandro J. Da Silva Sanchez, Curtis Dobrowolski, Ana Cristian, Elisa Schrader Echeverri, Kun Zhao, Marine Z. C. Hatit, David Loughrey, Kalina Paunovska, James E. Dahlman
Summary: In order to predict the effectiveness of lipid nanoparticle (LNP) delivery systems in humans, researchers have investigated whether the mechanism of LNP uptake into cells is consistent across different species. Studies have shown that besides the interaction between apolipoprotein E (ApoE) and low-density lipoprotein receptor (LDLR), other interactions may also affect the targeting ability of LNPs.
Article
Biochemistry & Molecular Biology
Han Zhang, Karen Kelly, Jonathan Lee, Dimas Echeverria, David Cooper, Rebecca Panwala, Nadia Amrani, Zexiang Chen, Nicholas Gaston, Atish Wagh, Gregory A. Newby, Jun Xie, David R. Liu, Guangping Gao, Scot A. Wolfe, Anastasia Khvorova, Jonathan K. Watts, Erik J. Sontheimer
Summary: This study demonstrates the use of chemical modification and protecting oligos to enhance the potency and stability of heavily modified crRNA in CRISPR-Cas9 genome editing. The co-delivery of chemically modified crRNAs with protecting oligos and AAV vectors enables in vivo genome editing in adult mouse liver and central nervous system, offering potential for transient editing activity and target multiplexing.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Yuan Rui, David R. Wilson, Stephany Y. Tzeng, Hannah M. Yamagata, Deepti Sudhakar, Marranne Conge, Cynthia A. Berlinicke, Donald J. Zack, Anthony Tuesca, Jordan J. Green
Summary: Nanoparticle-based mRNA therapeutics show great promise, but cellular internalization and endosomal escape pose challenges for cytosolic delivery. Researchers developed a dual nanoparticle uptake and endosomal disruption assay, which can detect cellular internalization and endosomal disruption. The study found that this assay has higher predictive capacity for mRNA delivery compared to conventional polymer and nanoparticle characteristics.
Article
Oncology
Jonathan Tucci, Ting Chen, Katherine Margulis, Etan Orgel, Rebecca L. Paszkiewicz, Michael D. Cohen, Matthew J. Oberley, Rachel Wahhab, Anthony E. Jones, Ajit S. Divakaruni, Cheng-Chih Hsu, Sarah E. Noll, Xia Sheng, Richard N. Zare, Steven D. Mittelman
Summary: The study found that adipocytes release free fatty acids in the presence of acute lymphoblastic leukemia cells, which are taken up by the leukemia cells and incorporated into triglycerides and phospholipids. Adipocyte-derived lipids can relieve ALL cell endogenous lipogenesis and reverse the cytotoxicity of chemotherapy, altering cell metabolism from glucose to fatty acid oxidation. Targeting lipid synthesis and metabolism may potentially reverse adipocyte protection of ALL cells.
FRONTIERS IN ONCOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Hongmei Liu, Chongyi Liu, Li Ye, Ding Ma, Xiaozhen He, Qianyun Tang, Xue Zhao, Hanbing Zou, Xiaojing Chen, Peifeng Liu
Summary: A novel PEG modification strategy was proposed in this study, forming PEG/G5PBA/siRNA nanoassemblies through reversible boronate esters, which significantly improved siRNA delivery efficiency under both serum-free and serum-containing conditions.
ADVANCED MATERIALS
(2021)
Article
Chemistry, Multidisciplinary
Tsogzolmaa Ganbold, Qingming Bao, Hai Xiao, Dolgorsuren Zurgaanjin, Caifeng Liu, Shuqin Han, Agula Hasi, Huricha Baigude
Summary: This study reports a novel lipid-nanoparticle-mediated delivery system for targeting TLR4 with siRNA, which successfully silences TLR4 in microglia and alleviates neuroinflammation. In a mouse model of ischemic stroke, this technique demonstrates significant neuroprotection.
Article
Multidisciplinary Sciences
Rakan El-Mayta, Marshall S. Padilla, Margaret M. Billingsley, Xuexiang Han, Michael J. Mitchell
Summary: Lipid nanoparticles (LNPs) have been successfully used in the development of COVID-19 mRNA vaccines, demonstrating the efficacy of mRNA-LNP therapeutics and opening up possibilities for future clinical applications. LNPs protect mRNA from degradation and facilitate intracellular delivery. In vitro and in vivo experiments evaluate the transfection efficiency of LNPs in cells and the luminescent flux in mice, providing representative results for their characteristics and efficacy.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Biophysics
Ismail Es, Antonio A. Malfatti-Gasperini, Lucimara Gaziola de la Torre
Summary: Our study investigated the manufacturing of lipid-based nanotherapeutics with stealth properties for siRNA delivery. The results showed that lipid nanocarriers had a bigger particle diameter and surface charge compared to lipoplexes. The inclusion of PEG-lipid resulted in an increase in the surface charge of lipoplexes, while a significant decrease was observed in the surface charge of lipid nanocarriers. Different structural assemblies were identified for lipoplex and lipid nanocarriers using Synchrotron SAXS.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2022)
Article
Pharmacology & Pharmacy
Hongqian Zhang, Feng Ding, Zongwei Zhu, Qian Sun, Chuanxu Yang
Summary: Small interfering RNA (siRNA) is a promising strategy for specific gene silencing in anti-inflammatory therapy. However, finding efficient carriers for delivering anti-inflammatory siRNA to macrophages remains challenging. In this study, we developed ionizable lipid nanoparticles (LNPs) with synthetic lipid-like materials to deliver siRNA to macrophages. By modifying the structure of synthetic lipid-like materials, we identified a potent LNP (1O14-LNP) that effectively transfects macrophages by promoting internalization and escape from endosomes. 1O14-LNP successfully delivered anti-inflammatory siRNA against interleukin-10 (siIL-10), resulting in significant downregulation of IL-10 expression in LPS-activated macrophages.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Medicine, Research & Experimental
Ryley Hall, Abdulaziz Alasmari, Saghar Mozaffari, Parvin Mandipoor, Keykavous Parang, Hamidreza Montazeri Aliabadi
Summary: Researchers developed a multicomponent delivery system called peptide lipid-associated nucleic acids (PLANAs) to encapsulate siRNA efficiently and achieve protein silencing in cancer cells.
MOLECULAR PHARMACEUTICS
(2021)
Article
Medicine, Research & Experimental
Xiaonan Huang, Ying Chau
Summary: Positively charged LNPs have demonstrated specific gene downregulation in the RGC layer, showing potential for the treatment of RGC-associated retinal diseases.
MOLECULAR PHARMACEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Masako Takatsu, Kunihiko Morihiro, Honoka Watanabe, Mizue Yuki, Takara Hattori, Kentaro Noi, Kohsuke Aikawa, Keiichi Noguchi, Masafumi Yohda, Takashi Okazoe, Akimitsu Okamoto
Summary: This study analyzed the cellular properties of DNA conjugates modified with perfluorocarbons (PFCs) and found that DNA conjugates with two or more PFC-containing units can penetrate cell membranes without causing damage. Furthermore, the modified DNA showed similar cell penetration and non-toxicity across different human cell lines, suggesting its potential as a nucleic acid delivery platform.
ACS CHEMICAL BIOLOGY
(2023)