APA
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Yoshinaga, N., Zhou, J. K., Xu, C., Quek, C., Zhu, Y., Tang, D., … Leong, K. W. (2023). Phenylboronic Acid-Functionalized Polyplexes Tailored to Oral CRISPR Delivery. Nano Letters (Print).
Chicago/Turabian
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Yoshinaga, Naoto, JoyceK Zhou, Cong Xu, C. Quek, Yuefei Zhu, Ding Tang, Lin Y. Hung, et al. “Phenylboronic Acid-Functionalized Polyplexes Tailored to Oral CRISPR Delivery.” Nano letters (Print) (2023).
MLA
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Yoshinaga, Naoto, et al. “Phenylboronic Acid-Functionalized Polyplexes Tailored to Oral CRISPR Delivery.” Nano Letters (Print), 2023.
BibTeX Click to copy
@article{naoto2023a,
title = {Phenylboronic Acid-Functionalized Polyplexes Tailored to Oral CRISPR Delivery.},
year = {2023},
journal = {Nano letters (Print)},
author = {Yoshinaga, Naoto and Zhou, JoyceK and Xu, Cong and Quek, C. and Zhu, Yuefei and Tang, Ding and Hung, Lin Y. and Najjar, Sarah A and Shiu, Chin Ying Angela and Margolis, K. and Lao, Yeh-Hsing and Leong, Kam W.}
}
Effective delivery of the CRISPR-Cas9 components is crucial to realizing the therapeutic potential. Although many delivery approaches have been developed for this application, oral delivery has not been explored due to the degradative nature of the gastrointestinal tract. For this issue, we developed a series of novel phenylboronic acid (PBA)-functionalized chitosan-polyethylenimine (CS-PEI) polymers for oral CRISPR delivery. PBA functionalization equipped the polyplex with higher stability, smooth transport across the mucus, and efficient endosomal escape and cytosolic unpackaging in the cells. From a library of 12 PBA-functionalized CS-PEI polyplexes, we identified a formulation that showed the most effective penetration in the intestinal mucosa after oral gavage to mice. The optimized formulation performed feasible CRISPR-mediated downregulation of the target protein and reduction in the downstream cholesterol. As the first oral CRISPR carrier, this study suggests the potential of addressing the needs of both local and systemic editing in a patient-compliant manner.
