Science Concentrates ENERGY STORAGE
C R E D I T: NAT UR E
Voltage loss in Li-ion batteries explained Low-cost electrodes that store more lithium than the ones used in today’s lithium-ion batteries could enable electric car drivers to go farther between charging stops. For that reason, researchers have examined many Li-based electrode materials, searching for better performers. A family of Li-rich layered transition metal oxides looks especially promising. Compared with common commercial electrode materials, these oxides could, in principle, store 30% or more charge on a volume basis. But the voltage of batteries made from these materials drops substantially with repeated charging. Understanding the electrochemical processes that cause these batteries to fail is key to overcoming this problem. By combining synchrotron-based X-ray microscopy, spectroscopy, and scattering techniques, researchers have now pinned down the complex interplay between changes in the crystal structure and redox potentials of Li1.17Ni0.21Co0.08Mn0.54O2, a member of the family of Li-rich layered oxides (Nat. Commun. 2017, DOI: 10.1038/s41467-017-02041-x). The material was prepared by chemists at Samsung, incorporated into battery cathodes, and analyzed via the X-ray methods by a large team that includes Michael F. Toney of SLAC National Accelerator Laboratory and Wanli Yang of Lawrence Berkeley National Laboratory. The analyses show that as lithium ions migrate from the cathode to the anode upon charging, transition metal ions move to fill the lithium vacancies, but not all of the metal ions move back during discharge. The incomplete ion shuttling leads to microscopic structural changes that alter oxygen’s bonding geometry, lowering oxygen’s redox potential and causing the drop in voltage.—MITCH JACOBY
Mouse cochlea with Tmc1 mutation-related damage (left) compared with one rescued by genome editing (right).
RARE DISEASE
Genome editing protects hearing in mice CRISPR-Cas9 technique reduces progressive hearing loss caused by rare genetic disease Researchers have used CRISPR-Cas9 genome editing to partially prevent hearing loss in mice with a genetic form of deafness. Traditional gene therapy, adding a functional gene to cells containing a missing or non-functional one, has been used before to treat genetic hearing loss in animals. But the new approach disrupts a bad gene instead of adding a good one. The study offers a possible treatment for a rare form of hearing loss in people caused by a single-base mutation in a gene called Tmc1. The mutation induces production of a protein that kills inner-ear hair cells, which sense sound waves. The mutation is dominant—a single mutation in one of the two gene copies causes people to lose hearing progressively. Traditional gene therapy cannot correct dominant mutations, so David R. Liu of Harvard University, Zheng-Yi Chen of Massachusetts Eye & Ear Infirmary and Harvard Medical School, and coworkers used CRISPR-Cas9 genome editing to cleave the mutated gene in mice (Nature 2017, DOI: 10.1038/nature25164). Eliminating the gene protects hair cells by preventing production of the toxic protein. To treat Tmc1-mutated newborn mice, the team combined Cas9 with guide RNA and a lipid. Cas9 is a nuclease that cuts double-stranded DNA, and the guide RNA has a sequence that directs Cas9 to the mutated gene but not the normal copy. The researchers injected the lipid complex into mouse inner-ear cochlea, where the
particles enter hair cells. In principle, such a delivery method could work in people. After several weeks, hair cells of treated mice looked full and normal, whereas those of untreated mice were damaged. Compared with untreated mice, the treated ones maintained a startle response to loud noises and scored more highly on hearing tests. They could hear about 15-decibel lower-intensity sounds, a substantial hearing improvement. Genetic therapies are realistic options for people “when hearing loss is progressive and intervention occurs prior to sensory hair cell damage,” says Karen Avraham of Tel Aviv University, whose group in 2002 discovered the Tmc1 mutation in hearing-impaired mice. “The key is to know what causes the deafness. Therefore, proper and early genetic diagnosis is essential for the approximately 50% of hearing loss cases that have a genetic cause.” The study shows that the genome therapy approach “is a plausible strategy to further develop,” says John V. Brigande of the Oregon Hearing Research Center at Oregon Health & Science University. Its strength “is that the disease gene is functionally knocked out, which is a permanent solution for successfully targeted cells.” However, in this study, probably fewer than 25% of hair cells had their mutated gene successfully knocked out. Therefore, he says, “it will be essential to maximize the efficiency of target cell editing to optimize therapeutic benefit.”—STU BORMAN JANUARY 1, 2018 | CEN.ACS.ORG | C&EN
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