Background Aging, noise, infection, and ototoxic drugs are the major causes of human acquired sensorineural hearing loss, but treatment options are limited. CRISPR/Cas9 technology has tremendous potential to become a new therapeutic modality for acquired non-inherited sensorineural hearing loss. Here, we develop CRISPR/Cas9 strategies to prevent aminoglycoside-induced deafness, a common type of acquired non-inherited sensorineural hearing loss, via disrupting the Htra2 gene in the inner ear which is involved in apoptosis but has not been investigated in cochlear hair cell protection. Results The results indicate that adeno-associated virus (AAV)-mediated delivery of CRISPR/SpCas9 system ameliorates neomycin-induced apoptosis, promotes hair cell survival, and significantly improves hearing function in neomycin-treated mice. The protective effect of the AAV–CRISPR/Cas9 system in vivo is sustained up to 8 weeks after neomycin exposure. For more efficient delivery of the whole CRISPR/Cas9 system, we also explore the AAV–CRISPR/SaCas9 system to prevent neomycin-induced deafness. The in vivo editing efficiency of the SaCas9 system is 1.73% on average. We observed significant improvement in auditory brainstem response thresholds in the injected ears compared with the non-injected ears. At 4 weeks after neomycin exposure, the protective effect of the AAV–CRISPR/SaCas9 system is still obvious, with the improvement in auditory brainstem response threshold up to 50 dB at 8 kHz. Conclusions These findings demonstrate the safe and effective prevention of aminoglycoside-induced deafness via Htra2 gene editing and support further development of the CRISPR/Cas9 technology in the treatment of non-inherited hearing loss as well as other non-inherited diseases.

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In a bounded domain Ω ⊂ R n with smooth boundary, this work considers the indirect pursuit-evasion modelwith positive parameters χ, ξ, λ, µ, a and b.It is firstly asserted that when n ≤ 3, for any given suitably regular initial data the corresponding homogeneous Neumann initial-boundary problem admits a global and bounded smooth solution. Moreover, it is shown that if bλ < µ and under some explicit smallness conditions on χ and ξ, any nontrival bounded classical solution converges to the spatially homogeneous coexistence state in the large time limit; if bλ > µ, however, then under an explicit smallness assumption on χ but without any restriction on ξ, any bounded classical solution (u, v) with u ≡ 0 stabilizes to (λ, 0) as t → ∞.1. Introduction. Lotka-Volterra type interplay, forming a class of paradigmatic interaction mechanisms in population dynamics, occurs in various biological and ecological processes, and the investigation of possible effects has been stimulated both theoretical biology and applied mathematics during the past century. A significant potential with regard to structure formation, preferably in contexts involving non-negligible migration of individuals, is indicated by numerous findings on colorful solution behavior already in simple reaction-diffusion systems combining Lotka-Volterra kinetics with undirected random diffusion ([15]).