In a thought-provoking Q&A with BioPharma BoardRoom, Demaris Mills, President of Integrated DNA Technologies (IDT), discusses the transformative advancements shaping gene editing and DNA synthesis as we approach 2025. From overcoming delivery challenges in CRISPR therapies to optimizing chemical gene synthesis for sustainability, Mills highlights IDT’s collaborative strategies and cutting-edge innovations. Explore how IDT is enabling breakthroughs in precision medicine while ensuring accessibility across established and emerging markets worldwide.

Q: As we look ahead to 2025, what technological advancements in gene editing do you foresee having the biggest impact on precision medicine?

A: A major area of development is the ongoing effort to develop CRISPR therapies that can be delivered to tissues of the body other than the liver, which is where most gene-editing treatments are targeted today. It’s challenging to deliver CRISPR to organs such as the brain and heart—but the ability to overcome those hurdles will expand the universe of diseases that can be addressed with gene editing, and ultimately the number of patients who can benefit from precision medicine. 

One promising partnership in this area was formed earlier this year between IDT’s parent company, Danaher, and the Innovative Genomics Institute (IGI) to launch the Danaher-IGI Beacon for CRISPR Cures. Our goal is to build platform technologies that can be expanded to the development of CRISPR treatments for about 500 genetic disorders known as "inborn errors of immunity" (IEIs). These disorders are not only amenable to being corrected with gene editing, but they also support a transplant-based route of CRISPR administration, which could help overcome the challenge of delivering gene-editing technology to specific tissues.

Another partnership, between Regeneron and Mammoth Biosciences, could also have a major impact on precision medicine. Those companies are developing a platform that uses Mammoth’s “ultracompact” gene-editing technology and Regeneron’s antibody-based targeting to develop next-generation viral delivery vectors. 

These are a few what could be several efforts resulting in CRISPR platform technologies in 2025, largely thanks to the FDA’s Platform Technology Designation Program for Drug Development Guidance for Industry. This pathway will allow developers to apply previously approved delivery vectors and gene-editing technologies to multiple CRISPR products. This will greatly shorten development timelines and speed the approval process for novel gene-editing products.

Q: How is Integrated DNA Technologies positioning itself to scale production while ensuring the highest standards of quality for gene synthesis?

A: IDT has introduced several innovations and optimizations for chemical gene synthesis, where DNA sequences are built one base at a time with phosphoramidite monomers. The four sequential chemical steps of this process—deprotection, coupling, capping, and oxidation—have built-in measures that help prevent the synthesis of undesired molecules and allow the correct DNA chain to continue to grow. With the optimizations that we have developed, IDT is able to achieve more than 99% coupling efficiency, which is quite high for bulk organic chemistry reactions. Furthermore, this synthesis route is unique in that it allows for the introduction of modifications that are crucial for the stability and efficacy of oligonucleotides as a therapeutic component. 

At the same time, we maintain the highest standard of quality with advanced purification procedures. Each cycle of DNA synthesis typically produces a tiny amount of unelongated products, which are terminated at the capping step. This prevents continued synthesis after a coupling failure, which in turn helps prevent internal deletions. It also eases purification after synthesis by making it easy to separate the short, failed synthesized genes from the desired full-length product. 

Improvements in chemical DNA synthesis are making the process more sustainable, as well. Over the past two decades, the output of IDT’s DNA synthesis technologies has increased significantly, making it possible to produce several times more DNA without expanding the footprint dedicated to the process. And some manufacturers are now recycling chemicals produced during DNA synthesis, which is reducing the amount of toxic waste produced during the process.

Q: What role does collaboration play in IDT’s strategy for developing cutting-edge nucleic acid technologies, and how do you see that evolving this year?

A: IDT works closely with customers and other Danaher operating companies to advance nucleic acid technologies. For example, we have worked with several developers of antisense oligonucleotides (ASOs), which are drugs that target RNA to alter gene expression. 

One area of research that’s rapidly evolving is the ability to improve the targeting of ASOs to boost their effectiveness. This is challenging, because ASOs are large compounds that are difficult to deliver to some target cells. There are ASO therapies on the market for Duchenne muscular dystrophy, but they have little impact on vital muscles such as the heart. And ASOs are difficult to develop for genetic diseases that affect brain development, because to be effective they have to be delivered via intrathecal injection. 

We are working closely with researchers on novel alternatives that could result in ASOs that can reach the brain, heart, and other tough-to-target tissues. Among the innovations in development are cell-penetrating peptides that can be attached to ASOs to improve tissue targeting, and ligands that can cross the blood-brain barrier following IV infusion. 

An important part of IDT’s strategy that will continue to evolve this year is our ability to provide end-to-end solutions through our collaborations with other Danaher companies. One customer that’s benefiting from those collaborations is Recursion, which is performing high-throughput, high-content genomic screening with whole-genome CRISPR library knockouts in a wide variety of settings. They knock out each gene one at a time, and then study the cells using confocal microscopy to determine cellular changes that are happening. Then they use artificial intelligence to create networks of interrelated genes and determine what genes would be most appropriate to focus on in a specific disease setting. They are getting CRISPR reagents from IDT, confocal imaging high- throughput systems from Molecular Devices, and robotics from Beckman Coulter. All of our contributions help optimize their workflow.

Q: With global health challenges in mind, what steps is IDT taking to ensure that its innovations are accessible to both established and emerging markets?

A: IDT continues to innovate solutions for streamlining laboratory workflows. For example, researchers can order from IDT several variations of genes in ready-to-use formats, which they can slot directly into automated workflows. We also introduced Rapid Genes, which are circular double-stranded DNA in plasmids. They can be shipped dry or in plates within five business days or faster, which is a big improvement over the typical turnaround time for synthetic genes.

Expanding our global footprint is also an important part of our effort to make our innovations more widely accessible in established and emerging markets. IDT serves customers in more than 100 countries, with facilities in Singapore, Japan, South Korea, Europe, and North America. In 2020. we launched IDT China to better serve our existing customer base in Asia and attract new customers. By providing access to our product portfolio, including xGen™ next generation sequencing (NGS) tools and solutions, we continue to support the efforts of researchers in China to develop precision medicines. 

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Demaris Mills’ insights highlight Integrated DNA Technologies’ pivotal role in driving technological and collaborative advancements that are shaping the future of precision medicine. As we approach 2025, IDT’s commitment to innovation, sustainability, and global accessibility underscores its dedication to empowering researchers and improving lives worldwide. At BioPharma BoardRoom, we are inspired by the transformative potential of IDT’s strategies and look forward to witnessing their impact on the evolving landscape of gene editing and nucleic acid technologies

( editor@biopharmaboardroom.com )