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<p>Human serum albumin (HSA) is critical for treating liver cirrhosis with ascites. However, plasma-derived HSA (pHSA) faces limitations in supply and carries potential infection risks. To address the urgent need for a therapeutically equivalent alternative, we established an efficient expression system for recombinant HSA (rHSA) in <i>Pichia pastoris</i>. We purified rHSA via a three-step chromatography purification process, yielding approximately 260&#xa0;mg per 1.5&#xa0;L of culture. Comprehensive analyses confirmed its structural equivalence to pHSA. Mass spectrometry revealed a molecular weight of 66,530.8 Da, while circular dichroism showed a 36.9% α-helical content. Furthermore, isothermal titration calorimetry demonstrated comparable drug-binding affinities for naproxen and warfarin. In a CCl₄-induced rat model of liver cirrhosis with ascites, rHSA displayed significant, dose-dependent therapeutic effects. Notably, high-dose rHSA achieved efficacy statistically equivalent to pHSA. It reduced ascites volume by 50.1%, improved liver index by 33.5% and restored colloid osmotic pressure along with liver function markers (ALT, AST, and bilirubin). This study provides the first <i>in vivo</i> evidence confirming the therapeutic equivalence and dose-effect relationship of <i>P. pastoris</i>-derived rHSA compared with pHSA. These findings establish a scalable, cost-effective, and safe platform for rHSA production, supporting its potential as a viable clinical substitute for plasma-derived albumin.</p>

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A Pichia pastoris-based platform for large-scale production of functional recombinant human serum albumin with therapeutic efficacy

  • 期刊论文

  • 发表日期：

    2026年7月13日

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  • Lijiong Li,
  • Jing Lin,
  • Mengfa Cui,
  • Hailong Fu,
  • Zhilin Wang

摘要

Human serum albumin (HSA) is critical for treating liver cirrhosis with ascites. However, plasma-derived HSA (pHSA) faces limitations in supply and carries potential infection risks. To address the urgent need for a therapeutically equivalent alternative, we established an efficient expression system for recombinant HSA (rHSA) in Pichia pastoris. We purified rHSA via a three-step chromatography purification process, yielding approximately 260 mg per 1.5 L of culture. Comprehensive analyses confirmed its structural equivalence to pHSA. Mass spectrometry revealed a molecular weight of 66,530.8 Da, while circular dichroism showed a 36.9% α-helical content. Furthermore, isothermal titration calorimetry demonstrated comparable drug-binding affinities for naproxen and warfarin. In a CCl₄-induced rat model of liver cirrhosis with ascites, rHSA displayed significant, dose-dependent therapeutic effects. Notably, high-dose rHSA achieved efficacy statistically equivalent to pHSA. It reduced ascites volume by 50.1%, improved liver index by 33.5% and restored colloid osmotic pressure along with liver function markers (ALT, AST, and bilirubin). This study provides the first in vivo evidence confirming the therapeutic equivalence and dose-effect relationship of P. pastoris-derived rHSA compared with pHSA. These findings establish a scalable, cost-effective, and safe platform for rHSA production, supporting its potential as a viable clinical substitute for plasma-derived albumin.