TY  - JOUR
AB  - We designed a unique nanocapsule for efficient single CRISPR-Cas9 capsuling, noninvasive brain delivery and tumor cell targeting, demonstrating an effective and safe strategy for glioblastoma gene therapy. Our CRISPR-Cas9 nanocapsules can be simply fabricated by encapsulating the single Cas9/sgRNA complex within a glutathione-sensitive polymer shell incorporating a dual-action ligand that facilitates BBB penetration, tumor cell targeting, and Cas9/sgRNA selective release. Our encapsulating nanocapsules evidenced promising glioblastoma tissue targeting that led to high PLK1 gene editing efficiency in a brain tumor (up to 38.1%) with negligible (less than 0.5%) off-target gene editing in high-risk tissues. Treatment with nanocapsules extended median survival time (68 days versus 24 days in nonfunctional sgRNA-treated mice). Our new CRISPR-Cas9 delivery system thus addresses various delivery challenges to demonstrate safe and tumor-specific delivery of gene editing Cas9 ribonucleoprotein for improved glioblastoma treatment that may potentially be therapeutically useful in other brain diseases.
AU  - Zou, Y
AU  - Sun, X
AU  - Yang, Q
AU  - Zheng, M
AU  - Shimoni, O
AU  - Ruan, W
AU  - Wang, Y
AU  - Zhang, D
AU  - Yin, J
AU  - Huang, X
AU  - Tao, W
AU  - Park, JB
AU  - Liang, X-J
AU  - Leong, KW
AU  - Shi, B
DA  - 2022/04/22
DO  - 10.1126/sciadv.abm8011
JO  - Sci Adv
PB  - AMER ASSOC ADVANCEMENT SCIENCE
PY  - 2022/04/22
SP  - eabm8011
TI  - Blood-brain barrier-penetrating single CRISPR-Cas9 nanocapsules for effective and safe glioblastoma gene therapy.
VL  - 8
Y1  - 2022/04/22
Y2  - 2026/06/04
ER  -