Selection of an Active Enzyme by Phage Display on the Basis of the Enzyme's Catalytic Activity in vivo

ChemBioChem ◽  
2005 ◽  
Vol 6 (2) ◽  
pp. 315-321 ◽  
Author(s):  
Satoshi Fujita ◽  
Takashi Taki ◽  
Kazunari Taira
Keyword(s):  
Catalytic Activity ◽  
Phage Display ◽  
Active Enzyme ◽  
Selection Of

scholarly journals Efficient In Vivo Selection of a Novel Tumor-Associated Peptide from a Phage Display Library

Molecules ◽  
2011 ◽  
Vol 16 (1) ◽  
pp. 900-914 ◽  
Author(s):  
Anka N. Veleva ◽  
Desh B. Nepal ◽  
C. Brandon Frederick ◽  
Jacob Schwab ◽  
Pamela Lockyer ◽  
...  
Keyword(s):  
Phage Display ◽  
Phage Display Library ◽  
In Vivo Selection ◽  
Selection Of

Selection of Metalloenzymes by Catalytic Activity Using Phage Display and Catalytic Elution

ChemBioChem ◽  
2001 ◽  
Vol 2 (4) ◽  
pp. 253-259 ◽  
Author(s):  
Isabelle Ponsard ◽  
Moreno Galleni ◽  
Patrice Soumillion ◽  
Jacques Fastrez
Keyword(s):  
Catalytic Activity ◽  
Phage Display ◽  
Selection Of

scholarly journals Efficient In Vivo Selection of a Novel Tumor-Associated Peptide from a Phage Display Library

Molecules ◽  
2011 ◽  
Vol 16 (1) ◽  
pp. 900-914 ◽  
Author(s):  
Anka N. Veleva ◽  
Desh B. Nepal ◽  
C. Brandon Frederick ◽  
Jacob Schwab ◽  
Pamela Lockyer ◽  
...  
Keyword(s):  
Phage Display ◽  
Phage Display Library ◽  
In Vivo Selection ◽  
Selection Of

Synchronous selection of homing peptides for multiple tissues by in vivo phage display

2006 ◽  
Vol 20 (7) ◽  
pp. 979-981 ◽  
Author(s):  
Mikhail G. Kolonin ◽  
Jessica Sun ◽  
Kim‐Anh Do ◽  
Claudia I. Vidal ◽  
Yuan Ji ◽  
...  
Keyword(s):  
Phage Display ◽  
In Vivo Phage Display ◽  
Selection Of

scholarly journals Highly Specific Blood-Brain Barrier Transmigrating Single-Domain Antibodies Selected by an In Vivo Phage Display Screening

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1598
Author(s):  
Sandra Isabel Aguiar ◽  
Joana N. R. Dias ◽  
Ana Santos André ◽  
Marta Lisete Silva ◽  
Diana Martins ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Phage Display ◽  
Blood Brain Barrier ◽  
Single Domain ◽  
Brain Barrier ◽  
The Brain ◽  
In Vivo Phage Display ◽  
Selection Of

A major bottleneck in the successful development of central nervous system (CNS) drugs is the discovery and design of molecules that can cross the blood-brain barrier (BBB). Nano-delivery strategies are a promising approach that take advantage of natural portals of entry into the brain such as monoclonal antibodies (mAbs) targeting endogenous BBB receptors. However, the main selected mAbs rely on targeting broadly expressed receptors, such as the transferrin and insulin receptors, and in selection processes that do not fully mimic the native receptor conformation, leading to mistargeting and a low fraction of the administered dose effectively reaching the brain. Thus, there is an urgent need to identify new BBB receptors and explore novel antibody selection approaches that can allow a more selective delivery into the brain. Considering that in vitro models fail to completely mimic brain structure complexity, we explored an in vivo cell immunization approach to construct a rabbit derived single-domain antibody (sdAb) library towards BBB endothelial cell receptors. The sdAb antibody library was used in an in vivo phage display screening as a functional selection of novel BBB targeting antibodies. Following three rounds of selections, next generation sequencing analysis, in vitro brain endothelial barrier (BEB) model screenings and in vivo biodistribution studies, five potential sdAbs were identified, three of which reaching >0.6% ID/g in the brain. To validate the brain drug delivery proof-of-concept, the most promising sdAb, namely RG3, was conjugated at the surface of liposomes encapsulated with a model drug, the pan-histone deacetylase inhibitor panobinostat (PAN). The translocation efficiency and activity of the conjugate liposome was determined in a dual functional in vitro BEB-glioblastoma model. The RG3 conjugated PAN liposomes enabled an efficient BEB translocation and presented a potent antitumoral activity against LN229 glioblastoma cells without influencing BEB integrity. In conclusion, our in vivo screening approach allowed the selection of highly specific nano-antibody scaffolds with promising properties for brain targeting and drug delivery.

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