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.

Peptide and Protein Delivery Using New Drug Delivery Systems

2013 ◽  
Vol 30 (4) ◽  
pp. 293-329 ◽  
Author(s):  
Ashish Jain ◽  
Aviral Jain ◽  
Arvind Gulbake ◽  
Satish Shilpi ◽  
Pooja Hurkat ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Protein Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
New Drug

Bone Morphogenetic Protein Delivery Systems

Spine ◽  
2002 ◽  
Vol 27 (Supplement) ◽  
pp. S16-S23 ◽  
Author(s):  
Howard Seeherman ◽  
John Wozney ◽  
Rebecca Li
Keyword(s):  
Bone Morphogenetic Protein ◽  
Protein Delivery ◽  
Delivery Systems ◽  
Morphogenetic Protein

scholarly journals Extracellular Vesicles as Natural Nanosized Delivery Systems for Small-Molecule Drugs and Genetic Material: Steps towards the Future Nanomedicines

2015 ◽  
Vol 18 (3) ◽  
pp. 396 ◽  
Author(s):  
Mustafa Kotmakçı ◽  
Vildan Bozok Çetintaş
Keyword(s):  
Extracellular Vesicles ◽  
Small Molecule ◽  
Protein Delivery ◽  
Drug Loading ◽  
Genetic Material ◽  
Delivery Systems ◽  
Small Molecule Drugs ◽  
The Common ◽  
Therapeutic Protocols ◽  
Targeting Ability

A new platform for drug, gene and peptide-protein delivery is emerging, under the common name of “extracellular vesicles”. Extracellular vesicles (EVs) are 30-1000 nm-sized cell-derived, liposome-like vesicles. Current research on EVs as nano-delivery systems for small-molecule drugs and genetic material, reveal that these tiny, biologically-derived vesicles carry a great potential to boost the efficacy of many therapeutic protocols. Several features of EVs; from efficacy to safety, from passive to active targeting ability, the opportunity to be biologically or chemically labelled, and most importantly, their eobiotic origin make them promising candidate for development of the next generation personalized nanomedicines. The aim of this article is to provide a view on the current research in which EVs are used as drug/genetic material delivery systems. Their application areas, drug loading and targeting strategies, and biodistribution properties are discussed.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Predicting protein instability in sustained protein delivery systems using spectral-phase interference

Biomaterials ◽  
2012 ◽  
Vol 33 (6) ◽  
pp. 1929-1938 ◽  
Author(s):  
Nina Seidel ◽  
Johannes Sitterberg ◽  
Wolfgang Vornholt ◽  
Udo Bakowsky ◽  
Michael Keusgen ◽  
...  
Keyword(s):  
Protein Delivery ◽  
Delivery Systems ◽  
Spectral Phase ◽  
Phase Interference ◽  
Protein Instability
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