Author: Zhou, Tongqing ; Roark, Ryan S. ; Doria‐Rose, Nicole A. ; Kwong, Peter D. ; Tourtellott‐Fogt, Emily ; Rawi, Reda ; Chan, Payton ; Shen, Chen‐Hsiang ; Tsybovsky, Yaroslav ; Einav, Tal ; Olia, Adam S. ; Wang, Shuishu ; Nazzari, Alexandra F. ; Pegu, Amarendra ; Stephens, Tyler ; Bender, Michael F. ; O'Dell, Sijy ; Zhang, Baoshan ; Shapiro, Lawrence ; Chaudhary, Ridhi ; Xu, Jianliang ; Lin, Bob C. ; Yang, Eun Sung ; Morano, Nicholas C. ; Chen, Xuejun ; Casellas, Rafael ; Louder, Mark K. ; Teng, I‐Ting ; Merriam, Jonah S. ; Liu, Cuiping ; Kwon, Young Do ; Changela, Anita ; Becker, Jordan E. ; McKee, Krisha

AbstractBroadly neutralizing antibodies are proposed as therapeutic and prophylactic agents against HIV‐1, but their potency and breadth are less than optimal. This study describes the immunization of a llama with the prefusion‐stabilized HIV‐1 envelope (Env) trimer, BG505 DS‐SOSIP, and the identification and improvement of potent neutralizing nanobodies recognizing the CD4‐binding site (CD4bs) of vulnerability. Two of the vaccine‐elicited CD4bs‐targeting nanobodies, G36 and R27, when engineered into a triple tandem format with llama IgG2a‐hinge region and human IgG1‐constant region (G36×3‐IgG2a and R27×3‐IgG2a), neutralized 96% of a multiclade 208‐strain panel at geometric mean IC80s of 0.314 and 0.033 µg mL−1, respectively. Cryo‐EM structures of these nanobodies in complex with Env trimer revealed the two nanobodies to neutralize HIV‐1 by mimicking the recognition of the CD4 receptor. To enhance their neutralizing potency and breadth, nanobodies are linked to the light chain of the V2‐apex‐targeting broadly neutralizing antibody, CAP256V2LS. The resultant human‐llama bispecific antibody CAP256L‐R27×3LS exhibited ultrapotent neutralization and breadth exceeding other published HIV‐1 broadly neutralizing antibodies, with pharmacokinetics determined in FcRn‐Fc mice similar to the parent CAP256V2LS. Vaccine‐elicited llama nanobodies, when combined with V2‐apex broadly neutralizing antibodies, may therefore be able to fulfill anti‐HIV‐1 therapeutic and prophylactic clinical goals.

01 Jan 2022·Protein Expression and PurificationQ4 · BIOLOGY

Effect of Clp protease from Corynebacterium glutamicum on heterologous protein expression

Q4 · BIOLOGY

Article

Author: Yang, Yankun ; Bai, Zhonghu ; Liu, Xiuxia ; Wang, Xinyue ; Meng, Lihong

The protease present in a host may reduce the yield and biological activity of heterologous proteins. In this study, we used protease overexpression and deletion strategies to examine the effect of the Clp protease system in Corynebacterium glutamicum on the recombinant protein and to produce a highly efficient heterologous protein expression host. In this study, we identified seven genes in the Clp protease family in Corynebacterium glutamicum ATCC 13032 through bioinformatics analysis, and studied their effects on the enhanced green fluorescent protein (EGFP) reporter protein. The fluorescence intensity of the knockout strain was significantly higher, and the effect of the clpS deletion strain was the most obvious. To verify the universal effect of the lack of clpS, the excellent industrial strain C. glutamicum 1.15647 was transformed to form recombinant 15647-ΔclpS. Based on the results, 15647-ΔclpS had a more significant effect on improving protein expression. Furthermore, recombinant human teriparatide (rhPTH) and variable domain of heavy chain of heavy-chain antibody (VHH) were selected to verify the universal applicability of the knockout strain for expressing heterologous proteins. Accordingly, we found that protease deficiency could increase the production of heterologous proteins. Finally, through a large-scale fermentation, the 15647-ΔclpS strain was used to produce VHH. Its yield was approximately 530 mg/L, which was 65% higher than that of WT-15647. In this study, a host that could effectively increase heterologous protein expression was successfully obtained.

26 May 2021·ACS Applied Materials & InterfacesQ2 · MATERIALS SCIENCE

Oral Delivery of Parathyroid Hormone Using a Triple-Padlock Nanocarrier for Osteoporosis via an Enterohepatic Circulation Pathway

Q2 · MATERIALS SCIENCE

Article

Author: Lee, Dong Yun ; Shahriar, S. M. Shatil ; An, Jeong Man ; Hwang, Yong Hwa ; Lee, Yong-kyu ; Cho, Sungpil ; Hwang, Seung Rim

Intermittent subcutaneous (S.C.) injection of teriparatide [PTH (1-34)] is one of the effective therapies to cure osteoporosis. However, a long-term repeated administration of teriparatide by S.C. to the patients is highly challenging. Herein, a triple padlock nanocarrier prepared by a taurocholic acid-conjugated chondroitin sulfate A (TCSA) is designed to develop an oral dosage form of recombinant human teriparatide (rhPTH). Oral administration of TCSA/rhPTH to the bilateral ovariectomized (OVX) rats resulted in the recovery of the bone marrow density and healthy serum bone parameters from the severe osteoporotic conditions. Also, it enhanced new bone formation in the osteoporotic tibias. This triple padlock oral delivery platform overcame the current barriers associated with teriparatide administration and exhibited a promising therapeutic effect against osteoporosis.

100 Deals associated with Recombinant Teriparatide(Shanghai United Cell Biotech)

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Indication	Country/Location	Organization	Date
Osteoporosis, Postmenopausal	CN	Shanghai United Cell Biotechnology Co. Ltd.	22 Mar 2017

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