James E. Dahlman
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View article: Lipid Nanoparticle Library Screen Reveals Lymphatic Endothelial Cell-Targeting Lipid Nanoparticle for Delivering Vascular Endothelial Growth Factor C mRNA after Lymphatic Injury
Lipid Nanoparticle Library Screen Reveals Lymphatic Endothelial Cell-Targeting Lipid Nanoparticle for Delivering Vascular Endothelial Growth Factor C mRNA after Lymphatic Injury Open
Dysfunction of the lymphatic system following injury, disease, or cancer treatment can lead to lymphedema, a debilitating condition with no cure. Advances in targeted therapy have shown promise for treating diseases where conventional ther…
View article: Glycolipid nanoparticles target the spleen and detarget the liver without charge
Glycolipid nanoparticles target the spleen and detarget the liver without charge Open
Lipid nanoparticles (LNPs) formulated with a neutral helper lipid can deliver RNA to the liver in humans. However, clinically relevant delivery to other tissues has remained challenging. To avoid the liver, scientists often add antibodies …
View article: Scalable, Antibody-Free Lipid Nanoparticle Achieves Human HSPC-Selective mRNA Delivery In Vivo Without Conditioning
Scalable, Antibody-Free Lipid Nanoparticle Achieves Human HSPC-Selective mRNA Delivery In Vivo Without Conditioning Open
Cell and gene therapies for hematologic malignancies currently rely on mobilization, apheresis, ex vivo genetic manipulation, and reinfusion of engineered cells. This multistep process is associated with significant logistical and clinical…
View article: Microfluidic Device Type Improves Heart mRNA Delivery <i>In Vivo</i>
Microfluidic Device Type Improves Heart mRNA Delivery <i>In Vivo</i> Open
To improve lipid nanoparticle (LNP)-mediated delivery to nonliver tissues, scientists modify LNP chemistry or add targeting ligands. One underexplored alternative is to change the formulation process that creates the LNP. Here, we report t…
View article: Gastrointestinal delivery of mRNA lipid nanoparticles selectively targets the pancreas
Gastrointestinal delivery of mRNA lipid nanoparticles selectively targets the pancreas Open
Lipid nanoparticles (LNPs) administered parenterally often show poor localization to the gastrointestinal (GI) tract and pancreas. In addition, patients typically prefer orally administered drugs to those given intravenously. We therefore …
View article: Development of a microneedle patch for delivery of mRNA-lipid nanoparticles
Development of a microneedle patch for delivery of mRNA-lipid nanoparticles Open
mRNA delivered by microneedle patch (MNP) can enable painless delivery, reduced need for healthcare expertise, and improved thermostability. In this study, we investigated formulation and manufacturing approaches for developing MNPs that d…
View article: The effect of mRNA-lipid nanoparticle composition on stability during microneedle patch manufacturing
The effect of mRNA-lipid nanoparticle composition on stability during microneedle patch manufacturing Open
Messenger RNA (mRNA) encapsulated in lipid nanoparticles (LNPs) is a potent technology with broad applications. Microneedle patches (MNPs) can enhance the accessibility of mRNA-LNPs for vaccination or therapeutic applications. We evaluated…
View article: Lipid nanoparticle screening in nonhuman primates with minimal loss of life
Lipid nanoparticle screening in nonhuman primates with minimal loss of life Open
Understanding how well delivery in mice predicts delivery in nonhuman primates (NHPs) could make lipid nanoparticle (LNP) discovery more efficient. Yet, few LNP-mRNA drug candidates are tested in NHPs, in part because the experiments requi…
View article: <i>In utero</i> lipid nanoparticle delivery achieves robust editing in hematopoietic stem cells
<i>In utero</i> lipid nanoparticle delivery achieves robust editing in hematopoietic stem cells Open
In vivo genome editing for hematologic malignancies is limited by inefficient delivery of genome editors to hematopoietic stem cells (HSC) in the bone marrow. To overcome this limitation, we capitalized on the inherent liver tropism of lip…
View article: Nanoparticle delivery of a prodrug-activating bacterial enzyme leads to anti-tumor responses
Nanoparticle delivery of a prodrug-activating bacterial enzyme leads to anti-tumor responses Open
Most cancer patients diagnosed with late-stage head and neck squamous cell carcinoma are treated with chemoradiotherapy, which can lead to toxicity. One potential alternative is tumor-limited conversion of a prodrug into its cytotoxic form…
View article: Amelioration of a von Willebrand disease type 2B phenotype in vivo upon treatment with allele-selective siRNAs
Amelioration of a von Willebrand disease type 2B phenotype in vivo upon treatment with allele-selective siRNAs Open
Treatment options for the bleeding disorder von Willebrand disease type 2B (VWD2B) are insufficient and fail to address the negative effects of circulating mutant von Willebrand factor (VWF). The dominant-negative nature of VWD2B makes fun…
View article: The time course of <i>in vivo</i> cellular responses to LNPs
The time course of <i>in vivo</i> cellular responses to LNPs Open
Transcriptomic analysis undertaken at different timepoints can shed light on mRNA-LNP in vivo delivery dynamics.
View article: Lymphatic endothelial cell-targeting lipid nanoparticles delivering VEGFC mRNA improve lymphatic function after injury
Lymphatic endothelial cell-targeting lipid nanoparticles delivering VEGFC mRNA improve lymphatic function after injury Open
Dysfunction of the lymphatic system following injury, disease, or cancer treatment can lead to lymphedema, a debilitating condition with no cure. Advances in targeted therapy have shown promise for treating diseases where conventional ther…
View article: Impact of allele-selective silencing of von Willebrand factor in mice based on a single nucleotide allelic difference in von Willebrand factor
Impact of allele-selective silencing of von Willebrand factor in mice based on a single nucleotide allelic difference in von Willebrand factor Open
This study demonstrates the feasibility of allele-selective Vwf-silencing in a heterozygous setting, achieving a controlled close to 50% reduction of plasma VWF. The observed thromboprotection and absence of prolonged bleeding times underl…
View article: Cationic cholesterol-dependent LNP delivery to lung stem cells, the liver, and heart
Cationic cholesterol-dependent LNP delivery to lung stem cells, the liver, and heart Open
Adding a cationic helper lipid to a lipid nanoparticle (LNP) can increase lung delivery and decrease liver delivery. However, it remains unclear whether charge-dependent tropism is universal or, alternatively, whether it depends on the com…
View article: RNA delivery systems
RNA delivery systems Open
Due to its small size and lifelong optical transparency, the fish Danionella cerebrum is an emerging model organism in biomedical research. How can this small vertebrate under 12 mm length produce sounds over 140 dB? We found that it posse…
View article: Substituting Poly(ethylene glycol) Lipids with Poly(2‐ethyl‐2‐oxazoline) Lipids Improves Lipid Nanoparticle Repeat Dosing
Substituting Poly(ethylene glycol) Lipids with Poly(2‐ethyl‐2‐oxazoline) Lipids Improves Lipid Nanoparticle Repeat Dosing Open
Poly(ethylene glycol) (PEG)–lipids are used in Food‐and‐Drug‐Administration‐approved lipid nanoparticle (LNP)–RNA drugs, which are safe and effective. However, it is reported that PEG–lipids may also contribute to accelerated blood clearan…
View article: Multivalent Targeting of the Asialoglycoprotein Receptor by Virus‐Like Particles
Multivalent Targeting of the Asialoglycoprotein Receptor by Virus‐Like Particles Open
The asialoglycoprotein receptor (ASGPR) is expressed in high density on hepatocytes. Multivalent variants of galactosyl carbohydrates bind ASGPR with high affinity, enabling hepatic delivery of ligand‐bound cargo. Virus‐like particle (VLP)…
View article: Small interfering RNA–mediated allele-selective silencing of von Willebrand factor in vitro and in vivo
Small interfering RNA–mediated allele-selective silencing of von Willebrand factor in vitro and in vivo Open
An imbalance in von Willebrand factor (VWF) may either lead to bleeding (von Willebrand disease, VWD) or thrombosis. Both disorders have shortcomings in the currently available treatments. VWF itself could be a potential therapeutic target…
View article: Current challenges and future directions for engineering extracellular vesicles for heart, lung, blood and sleep diseases
Current challenges and future directions for engineering extracellular vesicles for heart, lung, blood and sleep diseases Open
Extracellular vesicles (EVs) carry diverse bioactive components including nucleic acids, proteins, lipids and metabolites that play versatile roles in intercellular and interorgan communication. The capability to modulate their stability, …
View article: The Transcriptional Response to Lung-Targeting Lipid Nanoparticles <i>in Vivo</i>
The Transcriptional Response to Lung-Targeting Lipid Nanoparticles <i>in Vivo</i> Open
Lipid nanoparticles (LNPs) have delivered RNA to hepatocytes in patients, underscoring the potential impact of nonliver delivery. Scientists can shift LNP tropism to the lung by adding cationic helper lipids; however, the biological respon…
View article: A systematic analysis of biotech startups that went public in the first half of 2021
A systematic analysis of biotech startups that went public in the first half of 2021 Open
Biotechnologies are being commercialized at historic rates. In 2020, 74 biotech startups went public through an Initial Public Offering (IPO), and 60 went through the IPO process in the first six months of 2021. However, the traits associa…