Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.

/pdf/principles-of-nanoparticle-design-for-overcoming-biological-4c2c5quqtc.pdf

Principles of nanoparticle design for overcoming biological barriers to drug delivery

A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption1,2. There are no antiviral drugs with proven clinical efficacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells. Here we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins that physically associated with each of the SARS-CoV-2 proteins using affinity-purification mass spectrometry, identifying 332 high-confidence protein–protein interactions between SARS-CoV-2 and human proteins. Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds). We screened a subset of these in multiple viral assays and found two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the sigma-1 and sigma-2 receptors. Further studies of these host-factor-targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19. A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.

/pdf/a-sars-cov-2-protein-interaction-map-reveals-targets-for-5d1m2n6hc1.pdf

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.

http://csmres.co.uk/cs.public.upd/article-downloads/Peptide-therapeutics-current-status-and-future-directions.pdf

Peptide therapeutics: current status and future directions.

The success of anticancer therapy is usually limited by the development of drug resistance. Such acquired resistance is driven, in part, by intratumoural heterogeneity - that is, the phenotypic diversity of cancer cells co-inhabiting a single tumour mass. The introduction of the cancer stem cell (CSC) concept, which posits the presence of minor subpopulations of CSCs that are uniquely capable of seeding new tumours, has provided a framework for understanding one dimension of intratumoural heterogeneity. This concept, taken together with the identification of the epithelial-to-mesenchymal transition (EMT) programme as a critical regulator of the CSC phenotype, offers an opportunity to investigate the nature of intratumoural heterogeneity and a possible mechanistic basis for anticancer drug resistance. In fact, accumulating evidence indicates that conventional therapies often fail to eradicate carcinoma cells that have entered the CSC state via activation of the EMT programme, thereby permitting CSC-mediated clinical relapse. In this Review, we summarize our current understanding of the link between the EMT programme and the CSC state, and also discuss how this knowledge can contribute to improvements in clinical practice.

EMT, CSCs, and drug resistance: the mechanistic link and clinical implications

COVID-19 has spread globally since its discovery in Hubei province, China in December 2019. A combination of computed tomography imaging, whole genome sequencing, and electron microscopy were initially used to screen and identify SARS-CoV-2, the viral etiology of COVID-19. The aim of this review article is to inform the audience of diagnostic and surveillance technologies for SARS-CoV-2 and their performance characteristics. We describe point-of-care diagnostics that are on the horizon and encourage academics to advance their technologies beyond conception. Developing plug-and-play diagnostics to manage the SARS-CoV-2 outbreak would be useful in preventing future epidemics.

Diagnosing COVID-19: The Disease and Tools for Detection

Gene therapy is finally poised to make a contribution to the treatment of debilitating, highly penetrant genetic diseases that have proved intractable to other regimens.

Gene therapy finds its niche

Testing kits delivered by courier and digital tools combine to battle the COVID-19 outbreak. Testing kits delivered by courier and digital tools combine to battle the COVID-19 outbreak.

Fast, portable tests come online to curb coronavirus pandemic.

General Hospital, now the scientific founder and CSO of Exosome Diagnostics, was first author on a study that found exosomes could contribute to tumor growth through the transport of mRNA, miRNA and angiogenic proteins—and that these could also provide blood-based diagnostic information (Nat. Cell Biol. 10, 1470– 1476, 2008). Their role as a vehicle for cell-to-cell communication is now generally accepted. “The most important thing to understand is exosomes go everywhere—they can enter almost any tissue,” Kalluri says. Exosomes are fairly inert, but they fuse with the cell membrane, deliver a payload and change the biology of the recipient cell—hence their potential as nanoscale drug delivery vehicles or gene therapy vectors. “These things behave a little like an enveloped virus,” says Codiak’s Williams, formerly executive vice president of R&D at Biogen. They even have potential as cancer vaccines, as exosomes derived from antigen-presenting cells contain intact major histocompatibility complexes and are capable of antigen presentation (J. Immunol. 193, 1006– 1011, 2014). Another key thread in the exosome diagnostics story is in pancreatic cancer. In a recent 250-patient study, Kalluri and colleagues found glypican-1 (GPC1), a cell surface proteoglycan, specifically enriched in circulating exosomes from individuals with pancreatic cancer. GPC1 Exosome cancer diagnostic reaches market

Exosome cancer diagnostic reaches market.

International teams worked at speed to make tests for the virus available in record time. International teams worked at speed to make tests for the virus available in record time.

Coronavirus and the race to distribute reliable diagnostics.

“Apparently, the human genome is much more sensitive to different ways of achieving happiness than are conscious minds.” Steven Cole, UCLA, who showed that people who self-identified as seekers of happiness through living a life of purpose have a gene expression profile favorable to the immune system, whereas hedonistic people, while claiming to be happy, had negative expression profiles. (UPI.com 1 August 2013) iPS cells in humans

Cormac Sheridan

Papers

Gene therapy finds its niche

Fast, portable tests come online to curb coronavirus pandemic.

Exosome cancer diagnostic reaches market.

Coronavirus and the race to distribute reliable diagnostics.

First Axl inhibitor enters clinical trials