Biparatopic anti-PCSK9 antibody enhances the LDL-uptake in HepG2 cells.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target to reduce lipids. In 2020, we reported a chimeric camelid-human heavy chain antibody VHH-B11-Fc targeting PCSK9. Recently, it was verified that VHH-B11 binds one linear epitope in the PCSK9 hinge region. To enhance its druggability, we have developed a novel biparatopic B11-H2-Fc Ab herein. Thereinto, surface plasmon resonance (SPR) confirmed the epitope differences in binding-PCSK9 among VHH-B11, VHH-H2 and the approved Repatha. Additionally, SPR revealed the B11-H2-Fc exhibits an avidity of approximately 0.036 nM for PCSK9, representing a considerable increase compared to VHH-B11-Fc (~ 0.69 nM). Moreover, we found the Repatha and B11-H2-Fc exhibited > 95% PCSK9 inhibition efficiency compared to approximately 48% for the VHH-Fc at 7.4 nM (P < 0.0005). Further, we verified its biological activity using the human hepatoma cells G2 model, where the B11-H2-Fc exhibited almost 100% efficiency in PCSK9 inhibition at only 0.75 µM. The immunoblotting results of low-density lipoprotein cholesterol (LDL-c) uptake assay also demonstrated the excellent performance of B11-H2-Fc on recovering the LDL-c receptor (LDLR), as strong as the Repatha (P > 0.05). These findings provide the first evidence of the efficacy of a novel Ab targeting PCSK9 in the field of lipid-lowering drugs.

Vertical directional coupling based grating emission engineering for optical phased arrays.

In this Letter, a novel, to the best of our knowledge, vertical directional coupling waveguide grating (VDCWG) architecture is proposed to increase the length of waveguide grating antennas for large aperture on-chip optical phased arrays (OPAs). In this new architecture, the grating emission strength is engineered by the vertical directional coupler, which provides additional degrees of design freedom. Theoretical analysis and numerical simulation show that the VDCWG can adjust the grating strength in the range of more than two orders of magnitude, corresponding to an effective grating length more than a centimeter. For proof-of-concept, a VDCWG antenna with a length of 1.5 mm is experimentally demonstrated. The grating strength is measured to be 0.17 mm-1, and the far-field divergence angle is 0.061°. A 16-channel OPA is also developed based on the proposed VDCWG, which proves the potential of the new architecture for large aperture OPAs.