 VRC07-523LS.V34, with three charge substitutions, had an observed in vivo half-life and an estimated human half-life of 10.8 and 60 days, respectively, versus 5.4 and 38 days for VRC07-523LS and retained functionality, neutralizing 92% of a 208-strain panel at a geometric mean IC80-1G ML. Another variant, N6LS.C49, with two charge substitutions, had an observed in vivo half-life and an estimated human half-life of 14.5 and 80 days, versus 9.0 and 44 days for N6LS, and neutralized 80% of 208-strains at a geometric mean IC80-1G ML. Since ARCH and LIES residues are prevalent in human antibodies, we propose substitution of select ARCH or LIES with ASP, GLN, GLU, or SIR in the framework region as a general means to improve PKF therapeutic antidepressants. This article was authored by Young D Kwon, Amarendra Pagu, Eun Sun Young, and others. We are article.tv, links in the description below.