| UV-A light |
genetically encoded photocaged
Tyr |
nanobody (all) |
cell biology, targeted delivery |
+ small modification,
format transferability, 10 000-fold affinity
change |
(9, 10) |
| |
|
|
|
– known binding residues, UV light |
|
| |
|
|
|
|
|
| blue light |
optical magnet split antibodies (optobodies) |
nanobody, scFv |
cell biology |
+ blue light, potentially reversible |
(12) |
| |
|
|
|
– transferability may be challenging |
|
| |
|
|
|
|
|
| blue light |
conformational modulation
via light-oxygen-voltage domain (optobinders) |
nanobody, monobody |
cell biology, affinity purification |
+ reversible, activation
or inactivation, blue light, 330-fold affinity increase
monobodies |
(11, 13) |
| |
|
|
|
– <6-fold affinity increase nanobodies |
|
| |
|
|
|
|
|
| oligonucleotide |
divalent peptide–dsDNA
lock |
IgG |
logic gating |
+ no genetic modification required, possible combination
with other stimuli |
(29) |
| |
|
|
|
– small affinity change, relative instability |
|
| |
|
|
|
|
|
| small molecules |
folded dihydrofolate reductase blocking CDRs (LAMAs) |
nanobody |
cell biology |
+ reversible, 1000-fold affinity change |
(33) |
| |
|
|
|
– transferability may be challenging |
|
| |
|
|
|
|
|
| small molecule |
conformational disruption
via cavity |
scFv (Fab) |
therapeutic |
+ no potentially immunogenic appendage |
(32) |
| |
|
|
|
– 10-fold affinity change |
|
| |
|
|
|
|
|
| pH decrease |
electrostatic repulsion
upon protonation |
IgG |
therapeutic |
+ reversible, increased antibody half-life, two antibodies
in clinical use |
(46) |
| |
|
|
|
– only applicable to IgGs (FcRn binding) |
|
| |
|
|
|
|
|
| pH decrease |
electrostatic repulsion upon protonation (ALTAs) |
antibody–drug conjugates |
therapeutic |
+ reversible, increased efficacy |
(38) |
| |
|
|
|
– only in tumors with low levels of FcRn |
|
| |
|
|
|
|
|
| protease activity |
N-terminal
epitope-mimetic masking peptide |
IgG, bispecific IgG, CAR-T (all) |
therapeutic, diagnostic |
+ up to 300000-fold affinity
change, advanced clinical trials, format transferability |
(58−61) |
| |
|
|
|
– complex fine-tuning of masking peptide affinity |
|
| |
|
|
|
|
|
| protease activity |
masking N-terminal coiled-coil domains |
IgG (Fab) |
therapeutic |
+ 750-fold affinity change, highly transferable across antigen specificities |
(73) |
| |
|
|
|
– only applicable to IgGs and Fabs |
|
| |
|
|
|
|
|
| antigen combination |
functional peptide recruited
by cage domain |
DARPINs,
scFvs (all) |
therapeutic, diagnostic |
+ complex Boolean
logic operations possible, modularity |
(94) |
| |
|
|
|
– complex multicomponent system, possible immunogenicity |
|
