Correction: A Cancer Specific Cell-Penetrating Peptide, BR2, for the Efficient Delivery of an scFv into Cancer Cells

Abstract

Cell-penetrating peptides (CPPs) have proven very effective as intracellular delivery vehicles for various therapeutics. However, there are some concerns about non-specific penetration and cytotoxicity of CPPs for effective cancer treatments. Herein, based on the cell-penetrating motif of an anticancer peptide, buforin IIb, we designed several CPP derivatives with cancer cell specificity. Among the derivatives, a 17-amino acid peptide (BR2) was found to have cancer-specificity without toxicity to normal cells. After specifically targeting cancer cells through interaction with gangliosides, BR2 entered cells via lipid-mediated macropinocytosis. Moreover, BR2 showed higher membrane translocation efficiency than the well-known CPP Tat (49-57). The capability of BR2 as a cancer-specific drug carrier was demonstrated by fusion of BR2 to a single-chain variable fragment (scFv) directed toward a mutated K-ras (G12V). BR2-fused scFv induced a higher degree of apoptosis than Tat-fused scFv in K-ras mutated HCT116 cells. These results suggest that the novel cell-penetrating peptide BR2 has great potential as a useful drug delivery carrier with cancer cell specificity.

David vs. Goliath: The Structure, Function, and Clinical Prospects of Antibody Fragments

“…The latter may be solved by addition of a cell-targeting ligand to the antibody fragment. This was elegantly demonstrated by the authors in [165], who fused a cancer-cell specific, 17-amino acid peptide (BR2) to anti-mutated K-ras scFv, and demonstrated significant and cancer-cell-selective effects in vitro.…”

Neurodevelopmental heterogeneity and computational approaches for understanding autism

“…Few studies have attempted cross-diagnostic classification across ASD and ADHD. One study, conducted by Lim and colleagues, reported high accuracy when discriminating ADHD from controls versus ASD (accuracy 85.2 vs. 79.3%) when applying a Gaussian process classification to gray matter volumetric data 55 . Another study considered both ASD and ADHD, but only compare each classification against controls and not with each other 56 .…”

mRNA Engineering for the Efficient Chaperone-Mediated Co-Translational Folding of Recombinant Proteins in Escherichia coli

“…To test our hypothesis that spatially tethering a molecular chaperone with a target protein facilitates correct protein folding, we utilized the Escherichia coli DnaK chaperone system for in vivo solubilization of structurally diverse and aggregation-prone proteins. The proteins of interest (POIs) were chosen with a large diversity, including human antibody (anti-Ras single chain variable fragment, ScFv [24]), its fusion form for targeted-drug delivery (ScFv fused to a antimicrobial peptide BR2, BR2-ScFv [25]), therapeutic protein (bone morphogenetic protein 2, BMP2 [26], leptin [27,28]), viral protease (HIV-1 protease, HIV1-Pr [29]), and metabolic enzymes from E. coli and yeast (UGD [30], UbiC [31], Adh1p [32]). These POIs have been reported to show high aggregation tendency when expressed in bacteria [25,33,34,35,36,37] or observed in our experiments.…”

“…A flexible (GGGGS) 2 linker was used in between KH3 and DnaJ or DnaK. Target recombinant protein genes were PCR amplified from various sources: scfv and br2-scfv from pBR2ScFv [25]; ugd and ubiC from BL21(DE3) genomic DNA; and adh1p from Saccharomyces cerevisiae genomic DNA. The hiv1-pr gene [71] was codon-optimized and constructed by recombinant PCR; and tliA was amplified from pTliA [72].…”