Addressing Bioprocess Challenges in Enzyme Development for Pharmaceuticals
The pharmaceutical industry is increasingly turning to biocatalysis and enzyme-based technologies to streamline manufacturing processes, reduce environmental impact, and enable the production of complex molecules with high selectivity. However, the development and production of high-performance enzymes - particularly those used in advanced applications like CRISPR-based genome editing - pose significant bioprocessing challenges.
One of the most critical hurdles is achieving high yields and purity at commercial scale, especially for enzymes that strongly interact with nucleic acids, such as CRISPR nucleases. These enzymes are difficult to express and purify efficiently, often resulting in poor scalability and inconsistent quality. Additionally, the industry demands cost-effective and reproducible processes that comply with stringent quality and regulatory requirements.
We recognise these challenges and have developed an integrated, technology-driven approach to enzyme development and bioprocess optimisation. Our recent success in producing highly pure CRISPR nucleases at significantly increased yields demonstrates our capability to overcome these obstacles - offering a reliable and scalable solution for pharmaceutical applications.
Enhancing CRSIPR Nuclease Production through Advanced Bioprocess Design
In the rapidly evolving field of genome editing, the production of CRISPR nucleases as ribonucleoproteins (RNPs) presents significant challenges, particularly due to their strong DNA/RNA binding characteristics. BRAINBiocatalysts Life Science Solutions has effectively addressed these challenges by developing an optimised bioprocess that significantly enhances production yields and enzyme purity
Optimised Microbial Expression for Increased Yields
Utilising our expertise in microbial expression technology, we selected an optimal Escherichia coli strain, designed an efficient expression cassette, and employed a suitable plasmid to establish a robust production system. Through systematic optimisation of key process parameters - including temperature, pH, induction timing, and feed composition across fermentation scales from 2L to 10L, we achieved a 100% increase in nuclease production yield.
Overcoming Purification Challenges
The inherent strong nucleic acid binding properties of CRISPR nucleases complicate their purification. To address this, we developed a scalable, multi-step purification process that achieves enzyme purity exceeding 95%. This high level of purity ensures the nucleases are suitable for commercial use as RNPs in pharmaceutical applications.
Collaborative Approach Driving Success
This achievement underscores the strength of interdisciplinary collaboration within BRAINBiocatalysts, integrating microbial strain development, bioprocess optimisation and analytical expertise. Our commitment to scientific exchange and shared objectives has been pivotal in delivering this innovative solution.
Comprehensive Bioprocess Solutions
We offer advanced bioprocess solutions that ensure superior enzyme purity and functionality. Our integrated approach, encompassing enzyme discovery, optimisation, and large-scale production, positions us as a valuable partner for industrial applications in the pharmaceutical sector.
By harnessing the combined strengths of combined strengths of BRAIN Biotech and Biocatalysts Ltd., we continue to provide innovative enzyme solutions tailored specifically for pharmaceutical applications, driving advancements in bioprocess design and enzyme development.
