By Jennifer Honeycutt, Executive Vice President, Life Sciences
The ability of scientists to rationally engineer organisms using synthetic biology, or “engineering biology” as I prefer to call it, has progressed greatly since high throughput molecular biology techniques became available. Recent rapid advances in our engineering biology capabilities are enabling scientific discovery and biomedical development, such as the generation of synthetic protein-based switches that respond to stimuli within seconds rather than minutes or an hour, and cell-free systems to help scalably manufacture medicines and diagnostics on demand. The biopharmaceutical industry is also rapidly advancing with heavy investment after successes such as the production of the diabetes medication, sitagliptin, by engineered enzymes, and the therapeutic product itself being engineered CAR-T cells like the oncology therapy, Kymriah (tisagenlecleucel).
But is biopharma ready to reap the rewards and realize the full potential of engineering biology? This new paradigm promises to provide new pathways to drug discovery and development, portable cell-free solutions for the scalable industrial biomanufacturing of medicines and diagnostics on demand, and new preclinical testing methods. Partnering with science and technology companies could be the key, as they possess the technical expertise to help biopharma and biotech companies navigate and solve the challenges unique to this rapidly advancing field.
Engineering Biology and CRISPR Engineering for Genomic Medicines
Take for example Ginkgo Bioworks, dubbed “the organism company” and a rising star in the engineering biology space, who supported Moderna with process optimization for the manufacture of their mRNA vaccines by specialized enzymes produced in engineered microbes, including the vaccine against COVID-19. They partnered with SCIEX to effectively beta test SCIEX’s then newly developed ECHO® MS system, with 50% of their mass spectrometry (MS) "strain test" being performed on the ECHO® MS. The system has opened up their possibilities to perform larger experiments and screens. The ECHO® MS system relies on innovative acoustic ejection technology that was initially developed by Beckman Coulter Life Sciences, to transfer liquids with high precision and flexibility using sound waves. Ginkgo Bioworks also support bioengineering efforts across industries, including, for example, a collaboration with Aldevron to make improvements in the manufacturing yield of vaccinia capping enzyme (VCE) used in the manufacturing of mRNA vaccines. SCIEX, Beckman Coulter Life Sciences, and Aldevron are Life Sciences companies of Danaher Corporation.
Another example of how Danaher science and technology companies can provide critical support for biopharma companies is that of Integrated DNA Technologies (IDT) and Dr Matthew Porteus, a highly regarded Stanford physician and scientist. Dr Porteus is using CRISPR to genetically engineer hematopoietic stem and progenitor cells as potential therapies for patients with single gene disorders, such as sickle cell disease (SCD). Off-target editing is a known problem with CRISPR nucleases, including SpCas9, the most commonly used CRISPR nuclease. To address this challenge, Dr Christopher Vakulskas, PhD, generated a high fidelity SpCas9 that in a ribonucleoprotein complex dramatically improved the specificity of the genome editing, which was then validated experimentally with Dr Porteus. Dr Porteus continues to use the IDT HiFi SpCas9 in his preclinical studies and a clinical grade (GMP) version of the same enzyme, SpyFi™ produced by Aldevron, in his clinical trial of an experimental therapy based on genome editing to correct the mutation in the β-globin (HBB) gene that causes SCD. Similarly, IDT have developed a high efficiency Cas12a CRISPR enzyme, which is being used by Editas Medicine for CRISPR gene editing in their clinical development programs.
Expanding the Engineering Solutions for Biopharma
While engineering biology leverages the application of computational engineering approaches to synthesize and program biological organisms, engineering principles can also be applied to other stages of the biopharma lifecycle. Danaher companies can tap into their engineering heritage to do precisely that – apply an engineering mindset to solve the problems of biopharma commercial development and scalable industrial manufacturing. Engineers and scientists typically have different approaches and goals. Scientists apply the scientific method to test a hypothesis in the pursuit of knowledge. Engineers work to produce concrete solutions to real world problems. Incorporating the latter approach can include the application of iterative, parallelized practices to develop and continuously improve efficient platform processes; and deliberative frameworks and systematic tools to better integrate goal-setting and interdependent problem-solving.
Engineering principles could thus help effect the industrialization of biology by providing novel and optimized solutions to manufacturing and other challenges, especially for genomic medicines. This approach would also help enable the development of processes and systems that take into account the entire drug development and manufacturing workflow from end-to-end. These increasingly platform approaches are the key to industrializing biology to discover, develop, and manufacture new therapies at scale.
Engineering biology is becoming the one of the most important skills in biopharma and working with science and technology companies, especially those with a successful background in industrial engineering, will help empower the industry to make the most of this marriage of sciences and make Biopharma 4.0 a reality.
Echo and Echo MS are trademarks or registered trademarks of Labcyte Inc. in the United States and other countries. Labcyte is a wholly-owned subsidiary of Beckman Coulter Life Sciences.
Jennifer Honeycutt, Executive Vice President, Life Sciences