To overcome this problem, researches on simultaneous disruption of both CXCR4 and CCR5 genes by ZFNs and CRISPR/SpCas9 in primary human CD4+ T cells had been conducted, and such strategies could protect cells from both R4- and R5-tropic HIV-1 infection [34, 71, 72]. Here, CCR5 is linked to HIV-1 infection.