1255792-05-2Relevant articles and documents
Cellular delivery and photochemical activation of antisense agents through a nucleobase caging strategy
Govan, Jeane M.,Uprety, Rajendra,Thomas, Meryl,Lusic, Hrvoje,Lively, Mark O.,Deiters, Alexander
, p. 2272 - 2282 (2013)
Antisense oligonucleotides are powerful tools to regulate gene expression in cells and model organisms. However, a transfection or microinjection is typically needed for efficient delivery of the antisense agent. We report the conjugation of multiple HIV TAT peptides to a hairpin-protected antisense agent through a light-cleavable nucleobase caging group. This conjugation allows for the facile delivery of the antisense agent without a transfection reagent, and photochemical activation offers precise control over gene expression. The developed approach is highly modular, as demonstrated by the conjugation of folic acid to the caged antisense agent. This enabled targeted cell delivery through cell-surface folate receptors followed by photochemical triggering of antisense activity. Importantly, the presented strategy delivers native oligonucleotides after light-activation, devoid of any delivery functionalities or modifications that could otherwise impair their antisense activity.
Photoswitchable CAR-T Cell Function In Vitro and In Vivo via a Cleavable Mediator
Zhang, Bo,Wang, Yan,Huang, Shenlong,Sun, Jiaqi,Wang, Min,Ma, Wenxiao,You, Yanbo,Wu, Ling,Hu, Jin,Song, Wei,Liu, Xudong,Li, Shengjie,Chen, Hua,Zhang, Guisheng,Zhang, Lihe,Zhou, Demin,Li, Lingjun,Zhang, Xuan
, p. 60 - 7,69 (2020/12/07)
Chimeric antigen receptor (CAR)-T-based therapeutics are a breakthrough in cancer treatment; however, they are hampered by constitutive activation, which leads to worrisome side effects. Engineering CAR-T cells to be as tightly controllable as possible remains a topic of ongoing investigation. Here, we report a photoswitchable approach that uses a mediator for the at-will regulation of CAR-T cells. This mediator carries dual folate and fluorescein isothiocyanate moieties tethered by an ortho-nitrobenzyl ester photocleavable linker. CAR-T cells were shown to be highly cytotoxic to targeted cells only in the presence of the mediator and acted in a dose-dependent manner. The toxicity of CAR-T cells can be rapidly terminated by cleavage of the mediator, and the effects of CAR-T cells can be activated again by resupplementation with the mediator without compromising tumor therapy. The approach described here provides a direction for enhancing the controllability of CAR-T cells and can likely be applied in other immunotherapies.CAR-T is a powerful technology for cancer therapy, but is largely limited by inherent controllability issues. Zhang et al. developed an accurate controllable approach based on the bond-cleavage chemistry combined with universal anti-FITC CAR-T cells, allowing the regulation of CAR-T cells in a switchable manner.
For the control of the chimeric antigen receptor of the T cell activation/inhibit the connecting arm and its application (by machine translation)
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, (2019/01/23)
The invention discloses a method for control CAR - T/inhibit the activation of the link arm, and one end of the cells containing the target [...] molecule, the other at one end and can be specific CAR - T cell identified with biological orthogonality of the part, and the middle of the can be biological orthogonal fracture chemical group coupling. This invention can realize the CAR - T cell from active to a resting state fast and flexible conversion, to CAR - T cell inhibiting the systematic and high efficiency. Adjusting has reversibility, not damage or kill some CAR - T cell, can realize the CAR - T cell from active to close and then to activate the flexible change, the overall functions of the treatment is not affected. (by machine translation)
Water-Soluble molecularly imprinted nanoparticles (MINPs) with tailored, functionalized, modifiable binding pockets
Awino, Joseph K.,Zhao, Yan
, p. 655 - 661 (2015/08/04)
Construction of receptors with binding sites of specific size, shape, and functional groups is important to both chemistry and biology. Covalent imprinting of a photocleavable template within surface-core doubly cross-linked micelles yielded carboxylic acid-containing hydrophobic pockets within the water-soluble molecularly imprinted nanoparticles. The functionalized binding pockets were characterized by their binding of amine- and acid-functionalized guests under different pH values. The nanoparticles, on average, contained one binding site per particle and displayed highly selective binding among structural analogues. The binding sites could be modified further by covalent chemistry to modulate their binding properties.
A heterobifunctional linker bearing azide-reactive alkyne and thiol-reactive maleimide connected with N-(2-Nitrobenzyl)imide to synthesize photocleavable diblock copolymers
Yamamoto, Shota,Nakahama, Seiichi,Yamaguchi, Kazuo
supporting information, p. 791 - 793 (2013/09/02)
A novel heterobifunctional linker 1 connected with photocleavable N-(2-nitrobenzyl)imide has been developed. Hydrophobic polystyrene (PS), hydrophilic poly(ethylene oxide) (PEO), and thermosensitive poly(N- isopropylacrylamide) (PNIPAM) containing thiol or azide at the terminal, synthesized by a living radical polymerization or a transformation of terminal functional groups, were coupled with the alkyne and maleimide protected as the furan adduct at both terminals of 1 to synthesize three types of photocleavable diblock copolymers in high yields.
