New perspectives in oral peptide and protein delivery: from nanocarrier design to in vivo effectiveness

Author(s):  
María Alonso-Sande ◽  
Noemi Stefania Csaba ◽  
María José Alonso
Keyword(s):  
Nano Letters ◽  
2020 ◽  
Vol 20 (12) ◽  
pp. 8600-8607 ◽  
Author(s):  
Jia Lv ◽  
Changping Wang ◽  
Hongru Li ◽  
Zhan Li ◽  
Qianqian Fan ◽  
...  
Keyword(s):  

2016 ◽  
Vol 28 (23) ◽  
pp. 8792-8799 ◽  
Author(s):  
Jing Chen ◽  
Yan Zou ◽  
Chao Deng ◽  
Fenghua Meng ◽  
Jian Zhang ◽  
...  

2019 ◽  
Vol 5 (12) ◽  
pp. eaay3255 ◽  
Author(s):  
Yuan Rui ◽  
David R. Wilson ◽  
John Choi ◽  
Mahita Varanasi ◽  
Katie Sanders ◽  
...  

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.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mariano Maffei ◽  
Chiara Morelli ◽  
Ellie Graham ◽  
Stefano Patriarca ◽  
Laura Donzelli ◽  
...  

AbstractGene delivery using vector or viral-based methods is often limited by technical and safety barriers. A promising alternative that circumvents these shortcomings is the direct delivery of proteins into cells. Here we introduce a non-viral, ligand-mediated protein delivery system capable of selectively targeting primary skin cells in-vivo. Using orthologous self-labelling tags and chemical cross-linkers, we conjugate large proteins to ligands that bind their natural receptors on the surface of keratinocytes. Targeted CRE-mediated recombination was achieved by delivery of ligand cross-linked CRE protein to the skin of transgenic reporter mice, but was absent in mice lacking the ligand’s cell surface receptor. We further show that ligands mediate the intracellular delivery of Cas9 allowing for CRISPR-mediated gene editing in the skin more efficiently than adeno-associated viral gene delivery. Thus, a ligand-based system enables the effective and receptor-specific delivery of large proteins and may be applied to the treatment of skin-related genetic diseases.


Biomaterials ◽  
2018 ◽  
Vol 182 ◽  
pp. 167-175 ◽  
Author(s):  
Jia Lv ◽  
Bingwei He ◽  
Jingwen Yu ◽  
Yitong Wang ◽  
Changping Wang ◽  
...  
Keyword(s):  

2013 ◽  
Vol 2 (6) ◽  
pp. 379 ◽  
Author(s):  
He Shen ◽  
Min Liu ◽  
Yu Chong ◽  
Jie Huang ◽  
Zhijun Zhang

2012 ◽  
Vol 157 (3) ◽  
pp. 383-390 ◽  
Author(s):  
S. Al-Qadi ◽  
A. Grenha ◽  
D. Carrión-Recio ◽  
B. Seijo ◽  
C. Remuñán-López

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