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...

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...

Hereditary transthryretin amyloidosis is a rare disease caused by mutations in the gene encoding the protein transthyretin (TTR), causing it to misfold into amyloid plaques, leading to debilitating symptoms. In 2018,...

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...

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...

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...

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 ...

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 ...

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...

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...

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...

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 ...

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 ...

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 ...

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...

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.

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,...

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...

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.

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 ...