Recombinase library sequencing. Escherichia coli

Current combination antiretroviral therapies (cART) efficiently suppress HIV-1 reproduction in infected humans. However, cART does not eradicate HIV-1 in the body, necessitating lifelong medication. Therefore, intervention with additional critical steps of the virus life cycle might be indispensible to ultimately achieve an HIV cure. The most direct approach in eradicating HIV-1 is the physical removal of the integrated provirus from infected cells. Here, we present the development of broad-range recombinase 1 (Brec1) that recognizes a 34 bp sequence present in long terminal repeats (LTRs) of the majority of HIV-1 strains and subtypes. Brec1 removes efficiently, precisely and safely the integrated provirus from infected cells. Moreover, Brec1 acts efficaciously on clinical HIV-1 isolates in vitro and in vivo, particularly in humanized mice that were “personalized” with patient-derived cells. Thus, Brec1 represents a novel and potent antiviral reagent permitting broad clinical application in the context of future curative HIV-1 therapy strategies.