Biotech

Why Danaher is Focusing on Genomic Medicines

(Discussing a world without disease at Danaher’s inaugural Genomic Medicine Summit were, from left to right, Vanessa Almendro, Vice President of Science and Technology and Head of Innovation at Danaher, Parker Moss, Chief Ecosystems and Partnership Officer for Genomics England, Wendy Benson, Chief Strategy and Innovation Officer at Rady Children’s Institute for Genomic Medicine, Robert Green, professor of Medicine at Harvard Medical School, Walter Kowtoniuk, partner at Third Rock Ventures and board member of MOMA Therapeutics, and Stanley Crooke, founder, chief executive officer and chairman of n-Lorem Foundation)

Authored by: Jose-Carlos Gutiérrez-Ramos (‘JC’) Danaher Corporation and Vanessa Almendro, Danaher Corporation

Imagine a world without disease. What used to be an aspirational end state is now closer to a reality thanks to the advances in technologies that allow us to understand how the genome shapes disease states, from onset, to risk and protection. On December 7, Danaher hosted its Genomic Medicines Summit, during which a deep slate of scientist luminaries proposed a range of strategies for making that vision a reality. In a call to action, our day-long program in Boston included panel discussions and keynote addresses, featuring Harvard professor and biotech entrepreneur George Church, University of Pennsylvania professor and CAR-T pioneer Carl June, Innovative Genomics Institute Director and Berkeley professor Fyodor Urnov, Stanford professor Matthew Porteus and other key pioneers in genomic medicines. Representatives of several genomics companies and investor groups also joined us for the Summit—the first such event ever staged by Danaher in its 38-year history.

Why Danaher, and why now? We believe genomic medicines, including cell and gene therapies, offer the greatest promise of curing the world’s most difficult-to-treat diseases. Our life sciences and diagnostic companies have the tools and knowhow to help biopharma innovators make progress toward the vision of a world without disease.

To unlock the value that genomic medicines have to offer, the biopharma industry will need to overcome several roadblocks, including patient identification when the therapeutic intervention is able to provide maximum clinical benefit, scalability of drug manufacturing, and timely intervention which are critical components' to maximize impact of these revolutionary modern medicines.

At the Danaher Genomic Medicines Summit we covered critical topics to enable a future where genomic medicines are broadly used.  Experts on newborn sequencing provided insights about technologies that will enable a future were eligible patients are identified at birth. Several panelists described novel solutions under development to improve DNA decoding and the ability to synthesize and deliver genomic medicines. And many participants agreed that, while manufacturing costs are falling, there is still a pressing need for new ways to improve manufacturing efficiencies, scalability and speed of manufacturing. As George Church discussed - the convergence of technological and social innovations will be vital to achieving all these improvements and revolutionizing health care. 

Jose-Carlos Guti é rrez-Ramos, Chief Science Officer at Danaher Corporation, kicked off the company’s inaugural Genomic Medicines Summit

(Jose-Carlos Gutiérrez-Ramos, Chief Science Officer at Danaher Corporation, kicked off the company’s inaugural Genomic Medicines Summit)

Architecting the Future of Human Health

The Danaher companies that presented at the Summit—Aldevron, Precision NanoSystems (PNI) and Integrated DNA Technologies (IDT)—offer a range of tools and services to support genomic medicine development and next-generation biomanufacturing. Additional Danaher companies that offer different solutions for genomic medicine discovery and development are Cytiva, Pall Corporation, and Beckman Coulter Life Sciences.

Aldevron specializes in plasmid DNA (pDNA), which is a critical raw material for all genomic medicine applications. The demand for pDNA has intensified the need to develop novel methods of manufacturing DNA. Traditional cell-based methods for amplifying nucleic acid in large quantities are costly and time-consuming, and they include sequences that are not required for therapeutic effect. Cell-free DNA amplification eliminates impurities typically associated with traditional processes.

Aldevron has been perfecting plasmid pDNA production for more than 20 years, using proprietary technology to manufacture cell-free DNA for a wide range of research, preclinical, clinical and diagnostic applications. Aldevron has developed a highly efficient enzymatic process to amplify and produce high-quality, circular, supercoiled DNA. This platform is well-suited for applications requiring fast turnaround, highly complex sequences and small-scale batches, such as autologous therapies.

CRISPR is a rapidly growing technology that could hold the key to correcting some genetic diseases. IDT supports all aspects of the laboratory workflow to perform CRISPR genome editing. It offers online design tools that help researchers select optimal guide RNAs (gRNAs) and recombinant proteins, including proprietary mutants of the Cas9 and Cas12a enzymes with enhanced specificity and performance. IDT also makes custom DNA templates for homology directed repair (HDR), NGS systems (rhAmpSeq) to characterize gene-editing events, including potential off-target effects, and online computational tools to process and visualize NGS data.

While CRISPR nuclease cleavage can routinely be achieved with efficiency exceeding 90%, use of HDR to build new gene content is less reliable and methods to improve HDR efficiency are needed. IDT has identified a small-molecule compound that inhibits nonhomologous end joining (NHEJ) and increases HDR rates when used in cell culture, and it has developed a novel peptide-based HDR enhancer that works by increasing the activity of the HDR pathway without compromising the function of the parallel NHEJ pathway. The small molecule NHEJ inhibitor and peptide HDR enhancer can be combined for an even greater boost to HDR efficiency than the use of either agent alone provides.

Lipid nanoparticles (LNPs) are a preferred delivery mechanism for genomic medicines. PNI uses a microfluidic-based approach to enable the controlled and precise assembly of LNPs, and it has developed a genetic medicine toolbox to simplify the transition from preclinical into clinical development and manufacturing. For example, PNI offers a novel LNP-based formulation that enables the delivery of messenger RNA (mRNA) to primary T cells to facilitate the multi-step gene modification and production of CAR-T therapies. This approach eliminates the need for viral vector and electroporation-based methods, which should significantly reduce cost of goods and enable more consistent manufacturing outcomes.

Beyond CAR-T therapies, PNI is working on a suite of novel formulations to enable both the ex vivo and in vivo gene modification of cells. In collaboration with Aldevron and IDT, PNI is also working on the development of new LNP formulations to enable the delivery of various therapeutic cargoes beyond mRNA, such as plasmid DNA and ribonucleoprotein (RNP).

Murali Venkatesan, head of Danaher Equity Ventures, moderated a panel on innovation at the Genomic Medicines Summit.

(Murali Venkatesan, head of Danaher Equity Ventures, moderated a panel on innovation at the Genomic Medicines Summit)

Supporting the growth of genomic medicines

Danaher is also advancing the field of genomic medicine by investing in medical and technical innovations in academia, via the Danaher Beacons, and in startups and biotech via its venture capital group, Danaher Venture. Danaher Venture has invested in over 50 companies across the fields of life sciences, biotechnology and bioprocessing, and diagnostics. The startups we invest in are benefiting from the genomics and life sciences expertise across Danaher and are partnering with us in different ways to drive scientific breakthroughs, generate new products and advance science and technology.

The future is bright for innovators in the rapidly growing field of genomic medicines. Danaher is proud to support these visionaries as they work towards a future in which any disease can be cured.

Vanessa Almendro is Vice President of Science and Technology, Head of Innovation at Danaher Corporation where she leads multiple initiatives to position Danaher at the forefront of innovation in science, technology, and medicine. Prior to Danaher, Vanessa held several leadership positions at Eisai, Cogen Immune Medicines, and Vertex Pharmaceuticals. Vanessa has a Ph.D. in biochemistry and molecular biology from the University of Barcelona, a Post-doc in Translational Medicine from the Dana Farber Cancer Institute, Harvard Medical School, and an Executive M.B.A. from MIT-Sloan.

Jose-Carlos Gutiérrez-Ramos (‘JC’) is Chief Science Officer of Danaher Corporation, responsible for setting Danaher Science and Technology strategy and its implementation. JC has held multiple global roles in industry where he oversaw multiple drug discovery teams, resulting in five marketed drugs. He has a Ph.D. in immunology from the University of Madrid and trained as an immunologist in Spain, Germany, and Switzerland. He started his academic career as Assistant Professor of Genetics at Harvard Medical School and has authored more than 150 peer-reviewed publications.

https://www.danaher.com/genomic-medicines-summit

The editorial staff had no role in this post's creation.