Table 2.
Small molecules with potential to cross blood-brain barrier (BBB)
| Small Molecule | System(s) | Crosses BBB? | References |
|---|---|---|---|
| 4-Hydroxytamoxifen (4-OHT) | Cre-controlled CRISPR (3C), 4-OHT with split FKBP/FRB system, 4-OHT-responsive intein for Cas9, ERT2-based iCas system, allosterically regulated Cas9 (arC9) | yes | Rotheneichner et al.101 |
| Doxycycline (DOX) | 2xTetO DOX-inducible sgRNA system, self-inactivating CRISPR (SiC), ObLiGaRe doxycycline inducible Cas9 (ODInCas9) | yes | Norrby et al.102 |
| Isopropyl β-d-1-thiogalactopyranoside (IPTG) | 2xTetO DOX-inducible sgRNA system | yes | Morton et al.103 and Ryan and Scrable104 |
| Rapamycin | split FK506 binding protein 12/FKBP rapamycin binding (FKBP/FRB) system | yes | Majumder et al.105 |
| Auxin | auxin-induced degron (AID) system | possibly, shown to work in Drosophila melanogaster | McClure et al.106 |
| Indole-3-acetic acid (IAA) | AID system | possibly (but highly unlikely to use because of toxicity) | Lin et al.,107 Chen et al.,108 Hąc-Wydro and Flasiński,100 and Puurunen et al.109 |
| 1-Naphthaleneacetic acid (NAA) | AID system | possibly, shown to work in Drosophila melanogaster | Lin et al.107 and Chen et al.108 |
| dTag-47 | dTag System | unknown | N/A |
| Asunaprevir | SMASh | no | Koduri et al.110 |
| Shield-1 | mutated FKBP12-derived destabilization domain | yes | Froschauer et al.111 |
The ability for small molecules to penetrate the BBB could be helpful for controlling genome editing in the central nervous system.