In vivo brain delivery of BBB-enabled iduronate 2-sulfatase in rats

Table 1 SPR-derived kinetics and affinities of VHHs and IDS fusion constructs

Construct	Man6P	Target	k_a (1/Ms)	k_d (1/s)	K_D (M)
IGF1R3H5		h-IGF1R	3.34E + 05	2.51E-03	7.51E-09
IDS		h-IGF1R	n.b.	n.b.	n.b.
IDS		r-IGF1R	n.b.	n.b.	n.b.
IGF1R3H5-IDS	-	h-IGF1R	7.19E + 04	2.89E-03	4.02E-08
IGF1R3H5-IDS	+	h-IGF1R	6.40E + 04	2.95E-03	4.61E-08
IGF1R3H5-IDS		r-IGF1R	n.d.	n.d.	n.d.
IGF1R3H5-IDS-HSA	+	h-IGF1R	3.96E + 04	3.07E-03	7.73E-08
IGF1R3H5-IDS-HSA	+	rh-IGF1R	4.58E + 04	3.86E-03	8.44E-08
M79		HSA	4.52E + 06	0.126	2.78E-08^#
M79		RSA	1.56E + 07	6.61E-02	1.58E-09^#
M79		h-IGF1R	n.b.	n.b.	n.b.
R28		HSA	1.14E + 06	1.33E-02	1.17E-08^#
R28		RSA	2.29E + 06	1.65E-03	7.21E-10^#
R28		h-IGF1R	n.b.	n.b.	n.b.
IGF1R3H5-IDS-M79		HSA	1.37E + 05	0.265	1.94E-06
IGF1R3H5-IDS-M79		RSA	1.30E + 05	4.36E-02	3.36E-07
IGF1R3H5-IDS-M79		h-IGF1R	n.d.	n.d.	n.d.
IGF1R3H5-IDS-R28		HSA	2.76E + 04	3.29E-02	1.19E-06
IGF1R3H5-IDS-R28		RSA	1.71E + 04	1.51E-03	8.81E-08
IGF1R3H5-IDS-R28		h-IGF1R	n.d.	n.d.	n.d.

IGF1R3H5, humanized VHH targeting insulin like growth factor 1 receptor (IGF1R); IDS, iduronate-2-sulfatase; HSA, human serum albumin (K573P); RSA, rat serum albumin; M79, VHH targeting serum albumin; R28, VHH targeting serum albumin; Man6P, mannose-6-phosphate; h-IGF1R, human IGF1R; r-IGF1R, rhesus IGF1R; n.b., no binding; n.d., not determined
^# Determined in van Faassen et al. 2020 [15]

ISSN: 2045-8118