NIH R01 · 2024
In vivo transformation of chimeric antigen receptor B cells for a functional cure of HIV
PROJECT SUMMARY Our laboratories have developed novel techniques for the editing B-cell receptors of human primary B cells. Using newly identified CRISPR/Cas proteins and innovative homology-directed repair templates, we can efficiently overwrite the endogenous variable heavy (VH) and variable light (VL) segments of a mature VDJ- recombined BCR with the variable genes of broadly neutralizing HIV antibodies (bNabs). Importantly, these variable genes are placed in their respective natural loci, and – excepting the new VH and VL segments – these edited B cells are indistinguishable from unmodified mature, naïve B cells. We describe these edited B cells as “chimeric antigen receptor B cells”,…
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