Updates on CRISPR-based gene editing in HIV-1/AIDS therapy

Although tremendous efforts have been made to prevent and treat HIV-1 infection,HIV-1/AIDS remains a major threat to global human health.The combination antiretroviral therapy(cART),although able to suppress HIV-1 replication,cannot eliminate the proviral DNA integrated into the human genome and thus requires lifelong treatment that may lead to various side effects.In recent years,clustered regularly interspaced short palindromic repeat(CRISPR)-associated nuclease 9(Cas9)related gene-editing systems have been developed and designed as effective ways to treat HIV-1 infection.However,new gene-targeting tools derived from or functioning like CRISPR/Cas9,including base editor,prime editing,SHERLOCK,DETECTR,PAC-MAN,ABACAS,pfAGO,have been developed and optimized for pathogens detection and diseases correction.Here,we summarize recent studies on HIV-1/AIDS gene therapy and provide more gene-editing targets based on studies relating to the molecular mechanism of HIV-1 infection.We also identify the strategies and potential applications of these new gene-editing technologies for HIV-1/AIDS treatment in the future.Moreover,we discuss the caveats and problems that should be addressed before the clinical use of these versatile CRISPR-based gene targeting tools.Finally,we offer alternative solutions to improve the practice of gene targeting in HIV-1/AIDS gene therapy.