Abstract

Brent Stockwell’s lab at Columbia University demonstrated the efficacy of a small molecule encapsulated in a PEG-PLGA nanoparticle for inducing a form of cell death called ferroptosis (discovered by the Stockwell Lab) in diffuse large B cell lymphoma (DLBCL) mouse models...

Alpha-1-antitrypsin (AAT) deficiency is a genetic disorder that produces inactive/defective AAT due to mutations in the SERPINA1 gene encoding AAT. This disease is associated with decreased activity of AAT in the lungs and deposition of excessive defective AAT protein in the l...

Lipid nanoparticles (LNPs) are currently the most clinically advanced nonviral carriers for the delivery of small interfering RNA (siRNA). Free siRNA molecules suffer from unfavorable physicochemical characteristics and rapid clearance mechanisms, ...

Mast cells are important immune cells that have significant roles in mediating allergy and asthma. Therefore, studying the molecular mechanisms regulating these and other processes in mast cells is important to elucidate. Methods such as lipofectio...

Macrophage hyperfunction or dysfunction is tightly associated with various diseases, such as osteoporosis, inflammatory disorder, and cancers. However, nearly all conventional drug delivery system (DDS) nanocarriers utilize endocytosis for ent...

Nanopharmaceuticals aim at translating the unique features of nano-scale materials into therapeutic products and consequently their development relies critically on the progression in manufacturing technology to allow scalable processes complying w...

Lipid nanoparticles (LNPs) containing short interfering RNA (LNP-siRNA) and optimized ionizable cationic lipids are now clinically validated systems for silencing disease-causing genes in hepatocytes following intravenous administration. However, t...

The development of safe and efficacious gene vectors has limited greatly the potential for therapeutic treatments based on messenger RNA (mRNA). Lipid nanoparticles (LNPs) formed by an ionizable cationic lipid (here DLin-MC3-DMA), helper lipids (di...

Lipid-based nanobiomaterials as liposomes and lipid nanoparticles (LNPs) are the most widely used nanocarriers for drug delivery systems (DDSs). Extracellular vesicles (EVs) and exosomes are also expected to be applied as DDS nanocarriers. The perf...

The advancement of nanotechnology toward more sophisticated bioinspired approaches has highlighted the gap between the advantages of biomimetic and biohybrid platforms and the availability of manufacturing processes to scale up their production. Th...

Controlling the size and narrow size distribution of polymer-based nanocarriers for targeted drug delivery is an important parameter that significantly influences their colloidal stability, biodistribution, and targeting ability. Herein, we report ...

A cytomegalovirus (CMV) vaccine that is effective at preventing congenital infection and reducing CMV disease in transplant patients remains a high priority as no approved vaccines exist. While the precise correlates of protection are unknown, neut...

The process of optimization and fabrication of nanoparticle synthesis for preclinical studies can be challenging and time consuming. Traditional small scale laboratory synthesis techniques suffer from batch to batch variability. Additionally, the p...

Previous studies have identified relevant genes and signalling pathways that are hampered in human disorders as potential candidates for therapeutics. Developing nucleic acid-based tools to manipulate gene expression, such as short interfering RNAs...

Here, we show how dynamic nuclear polarization (DNP) NMR spectroscopy experiments permit the atomic level structural characterization of loaded and empty lipid nanoparticles (LNPs). The LNPs used here were synthesized by the microfluidic mixing tec...

Vesicle formation by a staggered herringbone microfluidic mixer was investigated in comparison to a sonication-extrusion method. Experiments focused on the incorporation efficiency of lipid components, on dye entrapment efficiency, and on the barri...

microRNAs (miRNAs) are critical for neuronal function and their dysregulation is repeatedly observed in neurodegenerative diseases. Here, we implemented high content image analysis for investigating the impact of several miRNAs in mouse primary mot...

Cytokinesis can fail during normal postnatal liver development, leading to polyploid hepatocytes. We investigated whether inhibiting cytokinesis in the liver slows tumor growth without compromising the health of normal hepatocytes. We inhibited cyt...

Inborn errors of metabolism (IEMs) can be relatively straight forward to screen for and diagnose; these disorders however, have currently very limited options for treatment. Methylmalonic acidemia (MMA), is an IEM caused by complete or partial defi...

mRNA vaccines are rapidly emerging as a powerful platform for infectious diseases because they are well tolerated, immunogenic, and scalable and are built on precise but adaptable antigen design. We show that two immunizations of modified non-repli...

Polymeric nanoparticles are efficient drug delivery vehicles that can deliver a wide range of bioactive agents. Specifically, poly(lactic-co-glycolic acid) copolymer (PLGA) based nanoparticles are biocompatible and biodegradable and approved by the...

Modified mRNA vaccines have developed into an effective and well-tolerated vaccine platform that offers scalable and precise antigen production. Nevertheless, the immunological events leading to strong antibody responses elicited by mRNA vaccines a...

Gene delivery for the purpose of protein expression has been traditionally performed by electroporation or viral transduction of plasmid DNA. Plasmid delivery has numerous challenges as they could potentially integrate into host genome and require ...

Currently, clinically approved medicines with liposomal formulations have a combined annual revenue of approximately $100 million USD, but their difficult and expensive production methods make more widespread use prohibitive. Microfluidic devi...

Understanding the effect of liposome size on tendency for accumulation in tumor tissue requires preparation of defined populations of different sized particles. However, controlling the size distributions without changing the lipid composition is d...

Despite the wide therapeutic potential of RNA interference (RNAi), clinical progress has been slow with only a few examples of successful translation. Efficient knockdown of hepatic transthyretin (87%) in patients with transthyretin amyloidosis las...

Lipid-like nanoparticles (LLNs) have shown great promise for nucleic acid delivery. Recently, we have developed N¹,N³,N⁵-tris(2-aminoethyl)benzene-1,3,5-tricarboxamide (TT) derived li...

RNA is emerging as a potential therapeutic modality for the treatment of incurable diseases. Despite intense research, the advent to clinical utility remains compromised by numerous biological barriers, hence, there is a need for sophisticated deli...

Lately there has been intense effort to develop vaccines for Zika virus, in part due to the recently established link between Zika infection and congenital birth defects such as microcephaly and the rapid spread of Zika in Oceania and the Americas ...

The cystic cavity that develops following injuries to brain or spinal cord is a major obstacle for tissue repair in central nervous system (CNS). Here we report that injection of imidazole-poly (organophosphazenes) (I-5), a hydrogel with thermosens...

Efficient and safe delivery of the CRISPR/Cas system is one of the key challenges for genome-editing applications in humans. Herein, we designed and synthesized a series of biodegradable lipidlike compounds containing ester groups for the delivery ...

Small interfering RNAs (siRNA) have a broad potential as therapeutic agents to reversibly silence any target gene of interest. The clinical application of siRNA requires the use of safe and effective delivery systems. In this study, we investigated...

Lipid-polymer hybrid nanoparticles (NPs) are advantageous for drug delivery. However, their intracellular trafficking mechanism and relevance for oral drug absorption are poorly understood. In this study, self-assembled core-shell lipid-polymer hyb...

Metastatic and multidrug resistant (MDR) tumors are generally very challenging to treat; and while in many cancers early detection can increase the survival rate significantly, the mortality rates of advanced and metastasized cancers are still quit...

The swine influenza pandemic of 2009 and more recent zoonotic transmissions of several avian influenza subtypes to human populations punctuates the threat posed by new pathogens for which we have no pre-existing immunity. Traditional vaccines requi...

Polymer conjugation is an attractive approach for delivering insoluble and highly toxic drugs to tumors. However, most reports in the literature only disclose the optimal composition without emphasizing rational design or composition optimization t...

In Alzheimer's disease proteasome activity is reportedly downregulated, thus increasing it could be therapeutically beneficial. The proteasome-associated deubiquitinase USP14 disassembles polyubiquitin-chains, potentially delaying proteasome-depend...

In the recent years, Zika virus (ZIKV) infection has become a global health threat. This infection has been known to cause multiple symptoms in adults including myalgia and conjunctivitis. More recent studies have also linked ZIKV with congenital m...

Like most genetic disorders, Hemophilia B is caused by a mutation that leads to a dysfunctional protein. Hemophilia B patients are susceptible to life threatening bleeds when injured due to a clotting defect caused by a mutated coagulation fac...

Advances in molecular biology have led to great interest and potential in applying gene therapy to correct/ regulate expression of disease-related genes that are otherwise undruggable. Gene therapy is one of the great pillars of the newly emerging ...

The therapeutic applications of lipid nanoparticle (LNP) formulations of small interfering RNA (siRNA), are hampered by inefficient delivery of encapsulated siRNA to the cytoplasm following endocytosis.

The CRISPR/Cas (clustered regularly interspaced short palindromic repeat/CRISPR-associated protein) gene-editing tool allows for sequence-specific cuts to genomic DNA, which can result in permanent silencing of a gene, or replacement of gene sequen...

Multi-functional nanomaterials possess unique properties, facilitating both therapeutic and diagnostic applications among others. Herein, we developed dual-functional lipid-like nanoparticles for simultaneous delivery of mRNA and magnetic resonance...

Cytotoxic chemotherapeutic agents are used as the standard therapy for a range of significant cancers, but many of these drugs suffer from poor water solubility and low selectivity, limiting their clinical efficacy. To overcome these shortcomings, ...

Liposomes are lipid-based supramolecular assemblies that can be engineered into efficacious drug carriers. Typically described as bilayer systems with an aqueous core, liposomes can increase the therapeutic index of a given drug molecule by decreas...

Liposomes have been the centre of attention in research due to their potential to act as drug delivery systems. Although its versatility and manufacturing processes are still not scalable and reproducible.

Non-ionic surfactant vesicles (NISV) are colloidal particles that provide a useful delivery system for drugs and vaccines. One of the methods that is used for NISV preparation is microfluidics in which the lipid components dissolved in organic phas...

We compare the microfluidic manufacturing of polycaprolactone-block-poly(ethylene oxide) (PCL-b-PEO) nanoparticles (NPs) in a single-phase staggered herringbone (SHB) mixer and in a two-phase gas–liquid segmented mixer.

Lipid nanoparticles (LNPs) for drug-delivery applications are largely derived from natural lipids. Synthetic lipids, particularly those incorporating branched hydrocarbons and hyper-branched hydrocarbon architectures, may afford enhanced lipophilic...

A wide range of studies have shown that liposomes can act as suitable adjuvants for a range of vaccine antigens. Properties such as their amphiphilic character and biphasic nature allow them to incorporate antigens within the lipid bilayer, on the ...

Quantification of the lipid content in liposomal adjuvants for subunit vaccine formulation is of extreme importance, since this concentration impacts both efficacy and stability. In this paper, we outline a high performance liquid chromatography-ev...

Molecular self-assembly has enabled the fabrication of biologically inspired, advanced nanostructures as lipid-based nanovesicles (L-NVs). The oldest L-NVs, liposomes, have been widely proposed as potential candidates for drug delivery, diagnostic ...

Clone 9 cells have been reported to express only the GLUT1 facilitative glucose transporter; however, previous studies have not examined Clone 9 cells for GLUT3 content. The current study sought to profile the presence of glucose transporters in Cl...

Microfluidic devices are mircoscale fluidic circuits used to manipulate liquids at the nanoliter scale. The ability to control the mixing of fluids and the continuous nature of the process make it apt for solvent/antisolvent precipitation of drug-d...

Sclerostin is a protein secreted by osteocytes that is encoded by the SOSTgene; it decreases bone formation by reducing osteoblast differentiation through inhibition of the Wnt signaling pathway.

PCTAIRE1/CDK16/PCTK1 plays critical roles in cancer cell proliferation and antiapoptosis. To advance our previously published in vitro results with PCTAIRE1 silencing, we examined the in vivo therapeutic potential o...

This protocol outlines a high-content screening (HCS) platform for investigating the impact of microRNA (miRNA) expression on primary motor neurons in culture. Such a system is applicable to automated screening of cell morphology in response to dru...

Lipid nanoparticles (LNP) can provide a clinically effective method for delivering small interfering RNA (siRNA) to silence pathological genes in hepatocytes. The gene silencing potency of these LNP-siRNA systems has been shown ...

Cochleates have been of increasing interest in pharmaceutical research due to their extraordinary stability. However the existing techniques used in the production of cochleates still need significant improvements to achieve sufficiently monod...

Small interfering RNAs (siRNAs) therapeutics has advanced into clinical trials for liver diseases and solid tumors, but remain a challenge for manipulating leukocytes fate due to lack of specificity and safety issues. Leukocytes ingest pathogens an...

The androgen receptor plays a critical role in the progression of prostate cancer. Here, we describe targeting the prostate-specific membrane antigen using a lipid nanoparticle (LNP) formulation containing small interfering RNA (siRNA) designed to ...

Liposomes not only offer the ability to enhance drug delivery, but can effectively act as vaccine delivery systems and adjuvants. Their flexibility in size, charge, bilayer rigidity and composition allow for targeted antigen delivery via ...

Lipid-like nanoparticles (LLNs) have shown great potential for RNA delivery. Lipid-like compounds are key components in LLNs. In this study, we investigated the effects of local structural transformation of lipid-like compounds on delivery of messe...

To date, most neurodegenerative disorders remain difficult to treat since neither traditional pharmaceutical nor surgical interventions have proven effective for these diseases. Neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS...

Liver cancer is a deadly disease with limited intervention options. Tumour removal surgery and liver transplantation are extremely complicated and not always possible. Several small molecule drugs aimed to treat hepatocellular carcinoma (HCC) have ...

Delivery of therapeutic nucleic acids in general and small interfering RNAs (siRNAs) in particular although a relatively nascent area of research, has already overcome several technical and regulatory hurdles over past few years.

Despite progress in systemic small interfering RNA (siRNA) delivery to the liver and to solid tumors, systemic siRNA delivery to leukocytes remains challenging. The ability to silence gene expression in leukocytes has great potential for ...

Considering the heterogeneity of leukemic cells in patients, current treatment regimens of chemotherapy and bone marrow transplantation lack specificity and are associated with frequent relapses and severe adverse effects. Hence, there is a need to develop novel therapeutics t...

Lipid nanoparticle (LNP) formulations facilitate tumor uptake and intracellular processing through an enhanced permeation and retention effect (EPR), and currently multiple products are undergoing clinical evaluation.

Described first in the 1960s by Bangham1 and understood as a potential drug delivery system in the early 1970s,2−4 the liposome has since become integral to research and clinical applications in the field of nanomedicine.

The in vivo roles for even the most intensely studied microRNAs remain poorly defined. Here, analysis of mouse models revealed that let-7, a large and ancient microRNA family, performs tumor suppressive roles at the expense o...

Although messenger RNA (mRNA) therapeutics are useful for transiently expressing antibodies and proteins, antigen-specific immune responses make the systemic delivery of mRNA challenging.

Previous work has shown that lipid nanoparticles (LNP) composed of an ionizable cationic lipid, a poly(ethylene glycol) (PEG)lipid, distearoylphosphatidylcholine (DSPC), cholesterol, and small interfering RNA (siRNA) can be efficient...

Modulating T cell function by down-regulating specific genes using RNA interference (RNAi) holds tremendous potential in advancing targeted therapies in many immune-related disorders including cancer, inflammation, autoimmunity,...

Many chemotherapeutic anticancer agents target vital components of cell division and inhibit survival and growth of cancer cells. Anti-tubulin agents for example, target the microtubule complex formed during mitosis and result in cell apoptosis. Read More

Besides their well-described use as delivery systems for water-soluble drugs, liposomes have the ability to act as a solubilizing agent for drugs with low aqueous solubility. However, a key limitation in exploiting liposome technology is ...

In this paper, the MacVicar Lab used Neuro9 siRNA cell transfection nanoparticles (Neuro9-siRNA) prepared using the NanoAssemblr^TM Benchtop instrument to uncover the role of a specific chloride channel in cytotoxic edema, which is a...

Previous studies from this group have shown that limit size lipid-based systems—defined as the smallest achievable aggregates compatible with the packing properties of their molecular constituents—can be efficiently produced using a&nbs...

Glioblastoma multiform (GBM) is one of the most malignant forms of brain tumors with very few treatment options other than aggressive surgical removal and radiotherapy. While most conventional chemotherapeutics fail when it comes to GBM, it is anti...

In bone research and orthopedics, RNA-interference (RNAi) and nanotechnology can be applied to a vast array of conditions where bone formation needs to be enhanced, providing new options to treat old problems, from osteoporosis and bone tumors to n...

Liposomes are an established delivery system for therapeutics, but liposome production methods have suffered from issues relating to quality and scalability that must be overcome before liposomes can be widely employed in clinical applications.

Recently developed lipid nanoparticle (LNP) formulations of siRNA have proven to be effective agents for hepatocyte gene silencing following intravenous administration with at least three LNP-siRNA formulations in clinical trials.

The discovery of RNA interference (RNAi) in mammalian cells has created a new class of therapeutics based on the reversible silencing of specific disease-causing genes.

Metastatic castration-resistant prostate cancer (mCRPC) is an advanced form of prostate cancer with poor prognosis and very few treatment options. Fractures and bone pain due to loss of bone density caused by bone metastasis is highly prevalent, re...

The ability of leptin to improve metabolic abnormalities in models of leptin deficiency, lipodystrophy, and even type 1 diabetes is of significant interest. However, the mechanism by which leptin mediates these effects remains ill-defined.

Therapeutics based on small interfering RNA (siRNA) have a huge potential for the treatment of disease but requires sophisticated delivery systems for in vivo applications.

A simple, efficient, and scalable manufacturing technique is required for developing siRNA-lipid nanoparticles (siRNA-LNP) for therapeutic applications.

The ability to manipulate gene expression and regulation in neurons is an invaluable asset to advancement of neuroscience and developing therapeutics for neurological disorders. 

Technological advances in both siRNA (small interfering RNA) and whole genome sequencing have demonstrated great potential in translating genetic information into siRNA-based drugs to halt the synthesis of most disease-caus...

Lipid nanoparticles (LNP) are the leading systems for in vivo delivery of small interfering RNA (siRNA) for therapeutic applications.

Gene therapy can be the solution to treatment of many undruggable conditions. RNA interference (RNAi) has been identified as a powerful gene therapy tool which can regulate and improve defective biological pathways through downregulation of target ...

The potency of drug delivery systems can heavily rely on their ability to penetrate poorly vascularized tissues such as tumors, following intravenous administration. The drug delivery vehicle’s size greatly impacts this phenomenon.