Recombinant Human Albumin Engineering Service

Recombinant Human Albumin (rHA) is a critical component for stabilizing therapeutic proteins, vaccines, and drug delivery systems. The traditional supply from human plasma carries an inherent risk of viral contamination , requiring complex and costly screening. Furthermore, the preferred microbial host, yeast ( Pichia pastoris ), often introduces abnormal glycosylation to the secreted protein, which can affect its clinical safety and efficacy.

CD Biosynsis offers a dedicated synthetic biology service to overcome these production hurdles using the Pichia pastoris chassis. Our core strategy involves glycosylation engineering of Pichia pastoris to yield rHA that more closely resembles the human native protein. This is combined with the optimization of secretion signal peptides to maximize the efficiency of protein export into the medium. This dual focus aims to establish a safer, more efficient, and medically compliant production route for high-quality rHA.

Pain Points

Developing a safe and scalable rHA bio-production system is challenged by:

• Viral Contamination Risk: Plasma-derived Albumin requires extensive viral inactivation and screening , which adds significant cost and complexity to quality control.
• Abnormal Glycosylation: Although Albumin itself is non-glycosylated, the yeast host may incorrectly process or modify the protein, potentially leading to altered immunogenicity or half-life in vivo.
• Low Secretion Efficiency: Yeast hosts often suffer from inefficient secretion of heterologous proteins , leading to product accumulation inside the cell and low final yields in the medium.
• Protein Stability and Integrity: Achieving the correct disulfide bond formation and maintaining the native structural integrity of human albumin in the yeast environment can be difficult.

A cost-effective and clinically viable solution must ensure biological safety and maximize secretion efficiency.

Solutions

CD Biosynsis applies advanced yeast engineering to address the rHA quality and yield issues:

Glycosylation Engineering of Pichia pastoris

           

We employ gene editing to knock out native glycosylation genes in yeast and/or introduce human-like glycosylation pathways, aiming to prevent the addition of immunogenic sugar moieties.

Optimization of Secretion Signal Peptides

We screen and engineer novel or modified secretion signal peptides to improve the recognition and efficient translocation of the rHA protein across the endoplasmic reticulum (ER) and cell membrane.

ER Folding and Quality Control Enhancement

We manipulate ER resident chaperones and foldases to enhance disulfide bond formation and ensure correct folding, aiming for high structural integrity of the secreted rHA.

Protease Knockout for Stability

Key genes encoding extracellular proteases in P. pastoris are targeted for knockout to minimize rHA degradation during high-density fermentation.

This systematic approach is focused on overcoming safety and efficiency bottlenecks in rHA bioproduction.

Advantages

Our rHA engineering service is dedicated to pursuing the following production goals:

Virus-Free Production

Eliminates the risk of contamination associated with human plasma, leading to a safer, regulatory-compliant product . (Image of Virus-Free Production Icon)

Bio-Equivalence Potential

Glycosylation engineering aims to produce rHA with features that may be closer to the native human protein , essential for clinical use.

Enhanced Secretion Efficiency

Optimization of signal peptides and folding machinery is focused on maximizing the final yield of secreted product into the medium.

Scalable Manufacturing

Pichia pastoris is an established industrial organism, allowing the transition to large-scale, high-density fermentation with high feasibility.

Cost Reduction Potential

High yields and a cleaner production stream may potentially reduce downstream purification costs compared to plasma extraction.

We provide a biosynthetic platform aimed at overcoming the safety and efficiency challenges of rHA production.

Process

Our rHA strain engineering service follows a standardized, multi-stage research workflow:

• Glycosylation Pathway Engineering: Identify and knock out yeast genes responsible for non-human glycosylation (e.g., mannosyltransferases), and integrate human-like glyco-genes if required.
• Secretion Signal Optimization: Design and screen a library of novel and optimized signal peptides to select the one achieving the highest rHA secretion efficiency.
• ER Quality Control Tuning: Overexpress ER folding assistants and potentially modify the unfolded protein response (UPR) pathway to enhance folding integrity.
• Protease and Catabolite Knockout: Knock out host proteases to minimize product degradation and potentially engineer the host to maximize growth on alternative carbon sources.
• Fermentation Performance Validation: Test the final engineered Pichia strain in high-density fed-batch fermentation , measuring the final titer, yield, and purity.
• Result Report Output: Compile a comprehensive Experimental Report detailing genetic modifications, secretion efficiency, and a preliminary structural and glycosylation profile , supporting regulatory review.

Technical communication is maintained throughout the process, focusing on timely feedback regarding secretion efficiency and protein quality.

Explore the potential for scalable, safe rHA production. CD Biosynsis provides customized strain engineering solutions:

• Detailed Secretion Titer and Purity Analysis Report , illustrating the success of signal peptide optimization.
• Consultation on fermentation strategies optimized for high-density Pichia culture.
• Experimental reports include complete raw data on the protein's structural integrity and glycosylation profile , essential for regulatory submission.