Gene editing to treat genetic deafness: "Beethoven mice" experiment is effective

famous pianist Beethoven was completely deaf at the age of 32, and the damage was self-evident, he wrote in his will to his brother, "Just as the leaves withered, my life has become hollow." Although
cause of Beethoven's hearing loss is unknown, many cases show that deafness is actually associated with genetic DNA mutations, and there are currently nearly 100 known genes associated with deafness. But so far, there is little cure for slowing or reversing deafness. Two centuries after Beethoven's death, the technology to stop genetic factors causing deafness is getting closer to clinical.
A study led by Zheng-Yi Chen, an associate professor of otolaryngology at Harvard Medical School, and David R. Liu, a professor of chemistry and chemical biology at Harvard University and a core member of the Broad Institute in the United States, was published online in the internationally renowned journal
, using gene editing techniques to treat the genetic deafness of the TCM1 mutation "Beethoven mice" with good results.
the inner ear is the most important part of sound perception, in which the inner ear hair cells are the key to human hearing. Among them, TCM1 is an important part of mechanical conduction in inner ear hair cells, TCM1 protein in the inner ear hair cells on the formation of a channel, when the sound waves cause cile hair movement when the channel will open, and then calcium ions into the cell to generate electrical signals, electrical signals transmitted to the brain to form hearing.
TCM1 has a significant negative misalmonic mutation, which causes the single-channel current level and calcium permeability of inner ear hair cells to decrease, further leading to deafness after the sensorineural language (deafness after language formation). Typically, patients with TCM1 explicit mutations begin to become deaf gradually at the age of 10-15.
TCM1 explicit mutation means that only one mutation in a pair of equal genes can lead to loss of function, which can lead to deafness. This also makes the restoration of explicit protrusions a delicate task: the mutant gene must be indestruded, while preserving the wild type of gene. The difference in this pair of genes is only in one of the nucleotides. The mutated TCM1 became adenine nucleotide A at the location of a thymosin nucleotide T in the original wild type.
Chen and Liu team enabled the popular CRISPR-Cas gene editing technology. The team injected fat droplets containing Cas9 and RNA into the inner ear of a newborn TCM1 Beethoven mouse, which then fuses with the cells. After gene editing, adenine nucleotide A is knocked out in the mutant gene, which insulates the gene. But at the same time, the wild gene is retained to ensure the realization of normal hearing function.
team assessed that genetically edited mice had higher survival rates and lower thresholds for listening to brain-dry reactions. In addition, auditory reflexes improved, with gene-edited adult Beethoven mice showing panic when they heard sudden noises, but unedited mice did not respond.
paper concludes by pointing out that this therapeutic approach has potential for the treatment of normal chromosomal explicit genetic deafness associated with endothocyte dysfunction, and provides complementary strategies for anthogenic oligonucleotide therapy and RNA interference therapy. (Source: Yu News He Liping)