Editors' ChoiceQUARTERLY PICKS

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Science Translational Medicine  24 Jun 2020:
Vol. 12, Issue 549, eabd1437
DOI: 10.1126/scitranslmed.abd1437

Abstract

Four times a year, the Science Translational Medicine editors select recently published articles across the Science family of journals and highlight interesting translational ties. These short write-ups identify common links between disparate diseases; technologies and research approaches that could prove complementary; and biomedical insights that may inform therapies or treatments. This quarter’s articles cover algorithm-assisted diagnosis of disease, strategies to surmount the blood-brain barrier, therapeutic gene editing, progress toward SARS-CoV-2 vaccines, the body’s response to synthetic materials, and immunotherapies for brain tumors.

CORONAVIRUS

Defeating SARS-CoV-2

The best hope of combating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus pathogen that causes coronavirus disease 2019 (COVID-19), is to rapidly develop a safe and effective vaccine. Much attention has been focused on the SARS-CoV-2 spike protein, which enables the virus to infect the respiratory epithelial cells of its human host. Reporting in Science Translational Medicine, Ravichandran et al. compared the quality of antibodies generated in rabbits immunized with four different versions of the SARS-CoV-2 spike protein, determining that the spike protein’s receptor binding domain elicited neutralizing antibodies with the highest affinity. Taking vaccine development a step further, a pair of recent Science papers tested two vaccines by immunizing rhesus macaques and then assessing protection against infection after exposure to a challenge dose of SARS-CoV-2. Yu et al. demonstrated induction of neutralizing antibodies and a cellular immune response using a DNA vaccine encoding the full-length spike protein (and various shorter versions), with a robust reduction in viral titer after challenge. Meanwhile, Gao et al. showed that a purified whole-inactivated SARS-CoV-2 virus vaccine elicited robust production of neutralizing antibodies in immunized macaques and complete protection at the highest vaccine dose after challenge. The next step will be clinical testing of these two vaccine candidates in the human population. —OS

CANCER

Brainy approach to cancer immunity

Immunotherapies for treating cancer, typically based on adaptive immunity, have advanced rapidly but have not been very successful for tumors in the brain. Recently, Sarkar et al. and Zhang et al. identified nontraditional approaches for brain tumor immunotherapy by manipulating the innate immune system. Sarkar et al. used niacin to reprogram macrophages to help fight glioblastoma, a primary brain tumor. Zhang et al. instead focused on brain metastases from peripheral cancer and identified an intervention that blocks immunosuppressive neutrophils from entering the tumors in the brain. Both studies expand our understanding of anticancer immunity and offer promising leads for treating deadly brain tumors— alone or in combination with other therapies. —YN

GENE EDITING

Editing out disease

The idea that DNA can be altered in cells to correct genetic diseases seems fantastic, but as two recent articles demonstrate, gene editing is becoming a therapeutic reality. Yeh et al. used a new approach, cytosine base editing, to partially restore hearing in a mouse model of hereditary hearing loss due to Tmc1 mutation. Maxwell et al. used CRISPR/Cas9 to correct a diabetes-causing mutation in induced pluripotent stem cells from a patient with Wolfram Syndrome. These cells were then differentiated into pancreatic β cells, which provided enough insulin to treat diabetic mice for 6 months. Both studies open the possibility that gene editing could be used to correct these genetic diseases in humans. —MN

BLOOD-BRAIN BARRIER

Reaching the brain

Treating neurological disorders is complicated by the presence of the blood-brain barrier, a highly selective border of endothelial cells that isolates the brain from the periphery. In a joint effort, Ullman et al. and Kariolis et al. developed a transport system that delivers therapeutics to the brain by exploiting receptor-mediated transcytosis and successfully tested the system in mice and monkeys. Using a different method to deliver therapeutic genes to brain tumors, Curley et al. showed that a guided focused ultrasound system coupled with brain penetrating nanoparticles was effective in mice. These papers illustrate two approaches that can be used, and possibly combined, to deliver therapeutics selectively to the brain. —MM

BIOMATERIALS

Fighting what’s foreign

When placed in the body, medical devices composed of synthetic materials can elicit an inflammatory reaction known as the foreign body response, which ultimately results in the formation of a fibrous capsule around the device. Chung et al. identified interleukin 17–producing T cells and senescent stromal cells as driving factors in fibrous capsule formation around breast implants. Studying a type of material used in breast implants, Cheng et al. demonstrated that biomedical silicones adsorbed matrix proteins and stimulated rigidity sensing pathways in cells via surface stresses. To mitigate adverse immune responses, Li et al. developed biomimetic polymers that resisted protein adsorption and cell adhesion and had immunomodulatory properties. These three studies help uncover the mechanisms regulating host response to synthetic materials and identify potential therapeutic targets. —CC

DIAGNOSIS

Algorithms in attending

Genetic information can help doctors zero in on a patient’s diagnosis, but interpolating the massive amount of genetic information available and tying it to pathogenicity can be a challenge, let alone at scale. In this quarter of Science Translational Medicine, Birgmeier et al. built an automated pipeline that analyzes phenotypic information of patients with a suspected Mendelian disorder and parses scientific literature to rank candidate causative genes and potential diagnoses. Conversely, Knevel et al. built a tool that uses any genetic data already available at the initial clinic visit of a patient presenting with inflammatory arthritis to triage related rheumatic disease diagnoses. One paper starts with phenotype to pinpoint genotype, and the other vice versa; together they show the power of big data to assist doctors with diagnoses. —CAC

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