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Your search keyword '"Cullis, Pieter R."' showing total 39 results
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39 results on '"Cullis, Pieter R."'

13. Suppression of fibrin(ogen)-driven pathologies in disease models through controlled knockdown by lipid nanoparticle delivery of siRNA

Author

Juang, Lih Jiin, Hur, Woosuk S., Silva, Lakmali M., Strilchuk, Amy W., Francisco, Brenton, Leung, Jerry, Robertson, Madelaine K., Groeneveld, Dafna J., La Prairie, Bridget, Chun, Elizabeth M., Cap, Andrew P., Luyendyk, James P., Palumbo, Joseph S., Cullis, Pieter R., Bugge, Thomas H., Flick, Matthew J., and Kastrup, Christian J.

Published
2022
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15. A magnetic separation method for isolating and characterizing the biomolecular corona of lipid nanoparticles

Author

CDL Nanomedicine, Centraal Diagnostisch Laboratorium, Cancer, Circulatory Health, Francia, Valentina, Zhang, Yao, Cheng, Miffy Hok Yan, Schiffelers, Raymond M, Witzigmann, Dominik, Cullis, Pieter R, CDL Nanomedicine, Centraal Diagnostisch Laboratorium, Cancer, Circulatory Health, Francia, Valentina, Zhang, Yao, Cheng, Miffy Hok Yan, Schiffelers, Raymond M, Witzigmann, Dominik, and Cullis, Pieter R

Published
2024

16. Lipid nanoparticles and siRNA targeting plasminogen provide lasting inhibition of fibrinolysis in mouse and dog models of hemophilia A

Author

Strilchuk, Amy W., primary, Hur, Woosuk S., additional, Batty, Paul, additional, Sang, Yaqiu, additional, Abrahams, Sara R., additional, Yong, Alyssa S.M., additional, Leung, Jerry, additional, Silva, Lakmali M., additional, Schroeder, Jocelyn A., additional, Nesbitt, Kate, additional, de Laat, Bas, additional, Moutsopoulos, Niki M., additional, Bugge, Thomas H., additional, Shi, Qizhen, additional, Cullis, Pieter R., additional, Merricks, Elizabeth P., additional, Wolberg, Alisa S., additional, Flick, Matthew J., additional, Lillicrap, David, additional, Nichols, Timothy C., additional, and Kastrup, Christian J., additional

Published
2024
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19. Lipid Nanoparticle-Mediated Hit-and-Run Approaches Yield Efficient and Safe In Situ Gene Editing in Human Skin

Author

Bolsoni, Juliana, primary, Liu, Danny, additional, Mohabatpour, Fatemeh, additional, Ebner, Ronja, additional, Sadhnani, Gaurav, additional, Tafech, Belal, additional, Leung, Jerry, additional, Shanta, Selina, additional, An, Kevin, additional, Morin, Tessa, additional, Chen, Yihang, additional, Arguello, Alfonso, additional, Choate, Keith, additional, Jan, Eric, additional, Ross, Colin J.D., additional, Brambilla, Davide, additional, Witzigmann, Dominik, additional, Kulkarni, Jayesh, additional, Cullis, Pieter R., additional, and Hedtrich, Sarah, additional

Published
2023
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21. Induction of Bleb Structures in Lipid Nanoparticle Formulations of mRNA Leads to Improved Transfection Potency

Author

Cheng, Miffy Hok Yan, primary, Leung, Jerry, additional, Zhang, Yao, additional, Strong, Colton, additional, Basha, Genc, additional, Momeni, Arash, additional, Chen, Yihang, additional, Jan, Eric, additional, Abdolahzadeh, Amir, additional, Wang, Xinying, additional, Kulkarni, Jayesh A., additional, Witzigmann, Dominik, additional, and Cullis, Pieter R., additional

Published
2023
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22. Supplementary Table 1-2, Figures S1-4 from siRNA Lipid Nanoparticle Potently Silences Clusterin and Delays Progression When Combined with Androgen Receptor Cotargeting in Enzalutamide-Resistant Prostate Cancer

Author

Yamamoto, Yoshiaki, primary, Lin, Paulo J.C., primary, Beraldi, Eliana, primary, Zhang, Fan, primary, Kawai, Yoshihisa, primary, Leong, Jeffrey, primary, Katsumi, Hidemasa, primary, Fazli, Ladan, primary, Fraser, Robert, primary, Cullis, Pieter R., primary, and Gleave, Martin, primary

Published
2023
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24. Single pulse nanosecond laser‐stimulated targeted delivery of anti‐cancer drugs from hybrid lipid nanoparticles containing 5 nm gold nanoparticles

Author

Uzel, Antoine, Agiotis, Leonidas, Baron, André, Zhigaltsev, Igor V., Cullis, Pieter R., Kafshgari, Morteza Hasanzadeh, Meunier, Michel, Uzel, Antoine, Agiotis, Leonidas, Baron, André, Zhigaltsev, Igor V., Cullis, Pieter R., Kafshgari, Morteza Hasanzadeh, and Meunier, Michel

Abstract

Encapsulating chemotherapeutic drugs like doxorubicin (DOX) inside lipid nanoparticles (LNPs) can overcome their acute, systematic toxicity. However, a precise drug release at the tumor microenvironment for improving the maximum tolerated dose and reducing side effects has yet to be well-established by implementing a safe stimuli-responsive strategy. This study proposes an integrated nanoscale perforation to trigger DOX release from hybrid plasmonic multilamellar LNPs composed of 5 nm gold (Au) NPs clustered at the internal lamellae interfaces. To promote site-specific DOX release, a single pulse irradiation strategy is developed by taking advantage of the resonant interaction between nanosecond pulsed laser radiation (527 nm) and the plasmon mode of the hybrid nanocarriers. This approach enlarges the amount of DOX in the target cells up to 11-fold compared to conventional DOX-loaded LNPs, leading to significant cancer cell death. The simulation of the pulsed laser interactions of the hybrid nanocarriers suggests a release mechanism mediated by either explosive vaporization of thin water layers adjacent to AuNP clusters or thermo-mechanical decomposition of overheated lipid layers. This simulation indicates an intact DOX integrity following irradiation since the temperature distribution is highly localized around AuNP clusters and highlights a controlled light-triggered drug delivery system.

Published
2023

30. Anionic Lipid Nanoparticles Preferentially Deliver mRNA to the Hepatic Reticuloendothelial System

Author

Pattipeiluhu, Roy, Arias-Alpizar, Gabriela, Basha, Genc, Chan, Karen Y.T., Bussmann, Jeroen, Sharp, Thomas H., Moradi, Mohammad Amin, Sommerdijk, Nico, Harris, Edward N., Cullis, Pieter R., Kros, Alexander, Witzigmann, Dominik, Campbell, Frederick, Pattipeiluhu, Roy, Arias-Alpizar, Gabriela, Basha, Genc, Chan, Karen Y.T., Bussmann, Jeroen, Sharp, Thomas H., Moradi, Mohammad Amin, Sommerdijk, Nico, Harris, Edward N., Cullis, Pieter R., Kros, Alexander, Witzigmann, Dominik, and Campbell, Frederick

Abstract

Lipid nanoparticles (LNPs) are the leading nonviral technologies for the delivery of exogenous RNA to target cells in vivo. As systemic delivery platforms, these technologies are exemplified by Onpattro, an approved LNP-based RNA interference therapy, administered intravenously and targeted to parenchymal liver cells. The discovery of systemically administered LNP technologies capable of preferential RNA delivery beyond hepatocytes has, however, proven more challenging. Here, preceded by comprehensive mechanistic understanding of in vivo nanoparticle biodistribution and bodily clearance, an LNP-based messenger RNA (mRNA) delivery platform is rationally designed to preferentially target the hepatic reticuloendothelial system (RES). Evaluated in embryonic zebrafish, validated in mice, and directly compared to LNP–mRNA systems based on the lipid composition of Onpattro, RES-targeted LNPs significantly enhance mRNA expression both globally within the liver and specifically within hepatic RES cell types. Hepatic RES targeting requires just a single lipid change within the formulation of Onpattro to switch LNP surface charge from neutral to anionic. This technology not only provides new opportunities to treat liver-specific and systemic diseases in which RES cell types play a key role but, more importantly, exemplifies that rational design of advanced RNA therapies must be preceded by a robust understanding of the dominant nano–biointeractions involved.

Published
2022

31. Role of drug delivery technologies in the success of COVID-19 vaccines: a perspective

Author

Massachusetts Institute of Technology. Department of Chemical Engineering, Labouta, Hagar I., Langer, Robert, Cullis, Pieter R., Merkel, Olivia M., Prausnitz, Mark R., Gomaa, Yasmine, Nogueira, Sara S., Kumeria, Tushar, Massachusetts Institute of Technology. Department of Chemical Engineering, Labouta, Hagar I., Langer, Robert, Cullis, Pieter R., Merkel, Olivia M., Prausnitz, Mark R., Gomaa, Yasmine, Nogueira, Sara S., and Kumeria, Tushar

Abstract

The triumphant success of mRNA vaccines is a testimony to the important role drug delivery technologies have played in protecting billions of people against SARS-CoV-2 (or the Corona Virus Disease 2019; COVID-19). Several lipid nanoparticle (LNP) mRNA vaccines were developed and have been instrumental in preventing the disease by boosting the immune system against the pathogen, SARS-CoV-2. These vaccines have been built on decades of scientific research in drug delivery of mRNA, vaccines, and other biologicals. In this manuscript, several leading and emerging scientists in the field of drug delivery share their perspective on the role of drug delivery technologies in developing safe and efficacious vaccines, in a roundtable discussion. The authors also discussed their viewpoint on the current challenges, and the key research questions that should drive this important area of research.

Published
2022

33. Anionic Lipid Nanoparticles Preferentially Deliver mRNA to the Hepatic Reticuloendothelial System

Author

Pattipeiluhu, Roy, primary, Arias‐Alpizar, Gabriela, additional, Basha, Genc, additional, Chan, Karen Y. T., additional, Bussmann, Jeroen, additional, Sharp, Thomas H., additional, Moradi, Mohammad‐Amin, additional, Sommerdijk, Nico, additional, Harris, Edward N., additional, Cullis, Pieter R., additional, Kros, Alexander, additional, Witzigmann, Dominik, additional, and Campbell, Frederick, additional

Published
2022
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34. Simultaneous, Single-Particle Measurements of Size and Loading Give Insights into the Structure of Drug-Delivery Nanoparticles

Author

Kamanzi, Albert, primary, Gu, Yifei, additional, Tahvildari, Radin, additional, Friedenberger, Zachary, additional, Zhu, Xingqi, additional, Berti, Romain, additional, Kurylowicz, Marty, additional, Witzigmann, Dominik, additional, Kulkarni, Jayesh A., additional, Leung, Jerry, additional, Andersson, John, additional, Dahlin, Andreas, additional, Höök, Fredrik, additional, Sutton, Mark, additional, Cullis, Pieter R., additional, and Leslie, Sabrina, additional

Published
2021
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36. Lipid nanoparticle-mediated silencing of osteogenic suppressor GNASleads to osteogenic differentiation of mesenchymal stem cells in vivo

Author

Basha, Genc, Cottle, Andrew G., Pretheeban, Thavaneetharajah, Chan, Karen YT., Witzigmann, Dominik, Young, Robert N., Rossi, Fabio MV., and Cullis, Pieter R.

Abstract

Approved drugs for the treatment of osteoporosis can prevent further bone loss but do not stimulate bone formation. Approaches that improve bone density in metabolic diseases are needed. Therapies that take advantage of the ability of mesenchymal stem cells (MSCs) to differentiate into various osteogenic lineages to treat bone disorders are of particular interest. Here we examine the ability of small interfering RNA (siRNA) to enhance osteoblast differentiation and bone formation by silencing the negative suppressor gene GNASin bone MSCs. Using clinically validated lipid nanoparticle (LNP) siRNA delivery systems, we show that silencing the suppressor gene GNAS in vitroin MSCs leads to molecular and phenotypic changes similar to those seen in osteoblasts. Further, we demonstrate that these LNP-siRNAs can transfect a large proportion of mice MSCs in the compact bone following intravenous injection. Transfection of MSCs in various animal models led to silencing of GNASand enhanced differentiation of MSCs into osteoblasts. These data demonstrate the potential for LNP delivery of siRNA to enhance the differentiation of MSCs into osteoblasts, and suggests that they are a promising approach for the treatment of osteoporosis and other bone diseases.

Published
2022
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37. Lipid Nanoparticle-Mediated Hit-and-Run Approaches Yield Efficient and Safe In SituGene Editing in Human Skin

Author

Bolsoni, Juliana, Liu, Danny, Mohabatpour, Fatemeh, Ebner, Ronja, Sadhnani, Gaurav, Tafech, Belal, Leung, Jerry, Shanta, Selina, An, Kevin, Morin, Tessa, Chen, Yihang, Arguello, Alfonso, Choate, Keith, Jan, Eric, Ross, Colin J.D., Brambilla, Davide, Witzigmann, Dominik, Kulkarni, Jayesh, Cullis, Pieter R., and Hedtrich, Sarah

Abstract

Despite exciting advances in gene editing, the efficient delivery of genetic tools to extrahepatic tissues remains challenging. This holds particularly true for the skin, which poses a highly restrictive delivery barrier. In this study, we ran a head-to-head comparison between Cas9 mRNA or ribonucleoprotein (RNP)-loaded lipid nanoparticles (LNPs) to deliver gene editing tools into epidermal layers of human skin, aiming for in situgene editing. We observed distinct LNP composition and cell-specific effects such as an extended presence of RNP in slow-cycling epithelial cells for up to 72 h. While obtaining similar gene editing rates using Cas9 RNP and mRNA with MC3-based LNPs (10–16%), mRNA-loaded LNPs proved to be more cytotoxic. Interestingly, ionizable lipids with a pKa∼ 7.1 yielded superior gene editing rates (55%–72%) in two-dimensional (2D) epithelial cells while no single guide RNA-dependent off-target effects were detectable. Unexpectedly, these high 2D editing efficacies did not translate to actual skin tissue where overall gene editing rates between 5%–12% were achieved after a single application and irrespective of the LNP composition. Finally, we successfully base-corrected a disease-causing mutation with an efficacy of ∼5% in autosomal recessive congenital ichthyosis patient cells, showcasing the potential of this strategy for the treatment of monogenic skin diseases. Taken together, this study demonstrates the feasibility of an in situcorrection of disease-causing mutations in the skin that could provide effective treatment and potentially even a cure for rare, monogenic, and common skin diseases.

Published
2023
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38. Blood-Based Multiomics-Guided Detection of a Precancerous Pancreatic Tumor.

Author

Anwar MA, Keshteli AH, Yang H, Wang W, Li X, Messier HM, Cullis PR, Borchers CH, Fraser R, and Wishart DS

Subjects
Humans, Middle Aged, Biomarkers, Tumor blood, Early Detection of Cancer methods, Magnetic Resonance Imaging, Metabolomics methods, Multiomics, Precision Medicine methods, Proteomics methods, Female, Pancreatic Neoplasms diagnosis, Pancreatic Neoplasms blood, Pancreatic Neoplasms surgery, Pancreatic Neoplasms genetics, Precancerous Conditions diagnosis, Precancerous Conditions blood, Precancerous Conditions pathology
Abstract

Over a decade ago, longitudinal multiomics analysis was pioneered for early disease detection and individually tailored precision health interventions. However, high sample processing costs, expansive multiomics measurements along with complex data analysis have made this approach to precision/personalized medicine impractical. Here we describe in a case report, a more practical approach that uses fewer measurements, annual sampling, and faster decision making. We also show how this approach offers promise to detect an exceedingly rare and potentially fatal condition before it fully manifests. Specifically, we describe in the present case report how longitudinal multiomics monitoring (LMOM) helped detect a precancerous pancreatic tumor and led to a successful surgical intervention. The patient, enrolled in an annual blood-based LMOM since 2018, had dramatic changes in the June 2021 and 2022 annual metabolomics and proteomics results that prompted further clinical diagnostic testing for pancreatic cancer. Using abdominal magnetic resonance imaging, a 2.6 cm lesion in the tail of the patient's pancreas was detected. The tumor fluid from an aspiration biopsy had 10,000 times that of normal carcinoembryonic antigen levels. After the tumor was surgically resected, histopathological findings confirmed it was a precancerous pancreatic tumor. Postoperative omics testing indicated that most metabolite and protein levels returned to patient's 2018 levels. This case report illustrates the potentials of blood LMOM for precision/personalized medicine, and new ways of thinking medical innovation for a potentially life-saving early diagnosis of pancreatic cancer. Blood LMOM warrants future programmatic translational research with the goals of precision medicine, and individually tailored cancer diagnoses and treatments.

Published
2024
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39. Genetically engineered transfusable platelets using mRNA lipid nanoparticles.

Author

Leung J, Strong C, Badior KE, Robertson M, Wu X, Meledeo MA, Kang E, Paul M, Sato Y, Harashima H, Cap AP, Devine DV, Jan E, Cullis PR, and Kastrup CJ

Subjects
Humans, Rats, Animals, RNA, Messenger genetics, RNA, Messenger metabolism, Blood Donors, Blood Platelets metabolism, Hemostatics metabolism
Abstract

Platelet transfusions are essential for managing bleeding and hemostatic dysfunction and could be expanded as a cell therapy due to the multifunctional role of platelets in various diseases. Creating these cell therapies will require modifying transfusable donor platelets to express therapeutic proteins. However, there are currently no appropriate methods for genetically modifying platelets collected from blood donors. Here, we describe an approach using platelet-optimized lipid nanoparticles containing mRNA (mRNA-LNP) to enable exogenous protein expression in human and rat platelets. Within the library of mRNA-LNP tested, exogenous protein expression did not require nor correlate with platelet activation. Transfected platelets retained hemostatic function and accumulated in regions of vascular damage after transfusion into rats with hemorrhagic shock. We expect this technology will expand the therapeutic potential of platelets.

Published
2023
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