Cytosolic protein delivery via metabolic glycoengineering and bioorthogonal click reaction

2021 ◽  
Author(s):  
Ziyin Zhao ◽  
Zhimin Zhang ◽  
Shanzhou Duan ◽  
Xun Liu ◽  
Renxiang Zhou ◽  
...  
Keyword(s):  
Protein Delivery ◽  
Click Reaction ◽  
Cytosolic Protein ◽  
Metabolic Glycoengineering

Cytosolic protein delivery holds great potentials for the development of protein-based biotechnologies and therapeutics. Currently, cytosolic protein delivery is mainly achieved with the assistance of various carriers. Herein, we present...

Photoenhanced cytosolic protein delivery based on a photocleavable group-modified dendrimer

Nanoscale ◽  
2021 ◽  
Author(s):  
Yafei Li ◽  
Yang Zhou ◽  
Tianyi Wang ◽  
Kaiqi Long ◽  
Yaming Zhang ◽  
...  
Keyword(s):  
Protein Delivery ◽  
Delivery Systems ◽  
Cytosolic Protein

Numerous recently developed therapies have highlighted the advantages of using proteins as therapeutics. However, in many protein delivery systems, the complicated carrier designs, low loading content, and off-targeting phenomenon have...

scholarly journals Carboxylated branched poly(β-amino ester) nanoparticles enable robust cytosolic protein delivery and CRISPR-Cas9 gene editing

2019 ◽  
Vol 5 (12) ◽  
pp. eaay3255 ◽  
Author(s):  
Yuan Rui ◽  
David R. Wilson ◽  
John Choi ◽  
Mahita Varanasi ◽  
Katie Sanders ◽  
...  
Keyword(s):  
Protein Delivery ◽  
Gene Editing ◽  
Gene Knockout ◽  
Cell Types ◽  
Endosomal Escape ◽  
Biological Research ◽  
Amino Ester ◽  
Cytosolic Protein

Efficient cytosolic protein delivery is necessary to fully realize the potential of protein therapeutics. Current methods of protein delivery often suffer from low serum tolerance and limited in vivo efficacy. Here, we report the synthesis and validation of a previously unreported class of carboxylated branched poly(β-amino ester)s that can self-assemble into nanoparticles for efficient intracellular delivery of a variety of different proteins. In vitro, nanoparticles enabled rapid cellular uptake, efficient endosomal escape, and functional cytosolic protein release into cells in media containing 10% serum. Moreover, nanoparticles encapsulating CRISPR-Cas9 ribonucleoproteins (RNPs) induced robust levels of gene knock-in (4%) and gene knockout (>75%) in several cell types. A single intracranial administration of nanoparticles delivering a low RNP dose (3.5 pmol) induced robust gene editing in mice bearing engineered orthotopic murine glioma tumors. This self-assembled polymeric nanocarrier system enables a versatile protein delivery and gene editing platform for biological research and therapeutic applications.

scholarly journals A boronic acid–rich dendrimer with robust and unprecedented efficiency for cytosolic protein delivery and CRISPR-Cas9 gene editing

2019 ◽  
Vol 5 (6) ◽  
pp. eaaw8922 ◽  
Author(s):  
Chongyi Liu ◽  
Tao Wan ◽  
Hui Wang ◽  
Song Zhang ◽  
Yuan Ping ◽  
...  
Keyword(s):  
Boronic Acid ◽  
Protein Delivery ◽  
High Efficiency ◽  
Intracellular Delivery ◽  
Cytosolic Protein ◽  
Native Proteins ◽  
Cytosolic Delivery ◽  
Cas9 Protein ◽  
Cargo Proteins ◽  
Positively Charged

Cytosolic protein delivery is of central importance for the development of protein-based biotechnologies and therapeutics; however, efficient intracellular delivery of native proteins remains a challenge. Here, we reported a boronic acid–rich dendrimer with unprecedented efficiency for cytosolic delivery of native proteins. The dendrimer could bind with both negatively and positively charged proteins and efficiently delivered 13 cargo proteins into the cytosol of living cells. All the delivered proteins kept their bioactivities after cytosolic delivery. The dendrimer ensures efficient intracellular delivery of Cas9 protein into various cell lines and showed high efficiency in CRISPR-Cas9 genome editing. The rationally designed boronic acid–rich dendrimer permits the development of an efficient platform with high generality for the delivery of native proteins.

scholarly journals General Strategy for Direct Cytosolic Protein Delivery via Protein–Nanoparticle Co-engineering

ACS Nano ◽  
2017 ◽  
Vol 11 (6) ◽  
pp. 6416-6421 ◽  
Author(s):  
Rubul Mout ◽  
Moumita Ray ◽  
Tristan Tay ◽  
Kanae Sasaki ◽  
Gulen Yesilbag Tonga ◽  
...  
Keyword(s):  
Protein Delivery ◽  
General Strategy ◽  
Cytosolic Protein

Natural Polyphenols Augment Cytosolic Protein Delivery by a Functional Polymer

2019 ◽  
Vol 31 (6) ◽  
pp. 1956-1965 ◽  
Author(s):  
Chongyi Liu ◽  
Wanwan Shen ◽  
Bonan Li ◽  
Tianfu Li ◽  
Hong Chang ◽  
...  
Keyword(s):  
Protein Delivery ◽  
Functional Polymer ◽  
Natural Polyphenols ◽  
Cytosolic Protein
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