Scientists have used antisense oligonucleotides for in utero correction of a mouse model of the syndrome Usera. The result has been to restore the protein expression, the gene of which is mutated in this disease, and to improve the development of hair cells in the inner ear. Mice were superior hearing and coordination compared to control animals. The method potentially can be used for intrauterine treatment of disorders of the auditory and vestibular system. Article published in the journal Nucleic Acids Research.
Usher syndrome is a genetic disease in which children are born deaf and gradually lose their vision. This disease is the cause of half of cases of deaf-blindness, it is diagnosed in about five people out of 100 thousand. Treatment that could prevent or slow the development of the syndrome Usera does not exist.
The reason one forms of the syndrome usher (type 1c) — point mutation in the gene Harmonia. This protein is stereocilia — processes of the hair cells of the inner ear that can feel vibrations of the fluid caused by the sounds. Mutations in harmonine lead to the fact that hair cells can’t translate the mechanical signal into electrical and pass information to the neurons.
Scientists have successfully restored production of normal harmonin with antimyeloma therapy in the first days after birth in mice with the same mutation. Antisense oligonucleotides (ASO) are short polymers, which are associated with the area of RNA according to the principle of complementarity and prevent its maturation or translation. ASO-29 mutant blocks the area of RNA Harmonia. Due to a mutation in the RNA, an additional site of splicing, and in the process of maturation proteins cut the molecule incorrectly. ASO-29 closes the wrong splicing site of enzymes, and they work with the plot.
However, in the first days after birth, the auditory system in mice has not yet been formed and corresponds to the degree of development of the inner ear of the person 18 weeks of pregnancy. If the therapy is done later, it is ineffective. So, if we want to apply the campaign for human treatment, antisense nucleotides need to enter in utero, but this procedure should work on animals.