The landscape of genomic medicine is undergoing rapid transformation. According to a survey of hundreds of healthcare leaders conducted for GlobalData’s “State of the Biopharmaceutical Industry in 2024” report, genomics represents the most impactful industry trend for the coming year — building on momentum from previous years, and beating other major themes like decentralized trials and medical marijuana.[1]
Genomic research isn’t going anywhere, and its potential is yet to be fully realized. Increased prevalence of chronic illnesses, plummeting costs of DNA sequencing and growing funding for genomics are all helping related treatments to thrive. For example, GlobalData’s Sales and Consensus database shows the market for DNA- and RNA-based gene therapies for oncology — the largest single area of research — has been steadily increasing. It was valued at $1.4 billion in 2022, grew to $2.3 billion in 2023, and is forecast to reach $28 billion by 2029 at a CAGR of 52.3%.[2]
Behind these headlines, researchers and biopharmaceutical companies are pioneering new approaches to address some of the most challenging disease areas. Advances in multi-modal therapeutic approaches, for example, are rapidly ramping up.
In a recent discussion, Dr. Aravind Asokan, synthetic virologist and Professor at Duke University, and Clive Glover, Viral Vector Business Leader at Cytiva (now leading Cytiva’s Pall Medical business), dove into the benefits of multi-modality, analyzed some of the most exciting examples currently being tested, and talked about the benefits of industry and academic collaboration.
The Promise of Multi-Modality Therapeutics
What makes the genomic medicine space so interesting right now is that modalities are quickly converging to open the doors to exciting new therapeutic possibilities.
While lentiviral vectors remain the preferred choice for gene delivery in CAR T workflows, cell therapy researchers are also looking to non-viral technologies, such as electroporation and lipid nanoparticles (LNPs). Why are these alternatives garnering interest? Following the success of COVID-19 vaccines, LNPs, for example, are considered to be a clinically validated, market-ready, and cost-effective delivery option for nucleic acids. They’re scalable and can transfect many cells with high viability and yield, while offering a favorable overall safety profile. Together, these advantages could enhance T cell engineering strategies for the development of more precise and efficient CAR T cell therapies in the fight against cancer and other diseases.
There’s also research into different viral vectors for CAR T. Adeno-associated viruses (AAVs), engineered to deliver therapeutic genes to specific cells, have been extensively studied for gene therapy applications. Now, AAV is being considered as a way of generating CAR T cells in vivo to potentially eliminate time-consuming and invasive steps currently required for the ex vivo development of these treatments. “When it comes to editing machinery, there are many different ways to get that into T cells,” points out Dr. Asokan. “But if you want to integrate a piece of genome into T cells at high efficiency, what they call the ‘donor DNA AAV’ is still masterful at doing that across tissues.”
The convergence of AAVs and CRISPR technology is another exciting area of research. While AAVs are excellent for delivering genetic material, CRISPR offers a tool for precise gene editing. Together, they have the potential to provide comprehensive solutions for treating a wide range of genetic disorders. “With CRISPR being a multi-modality platform in itself, you’ve got the protein, you’ve got the RNA that’s supposed to take it to the target DNA, and you might still want to paste a piece of DNA in there.” But he adds, AAV is still masterful at delivering DNA. “There is a world where maybe we don’t just look at it as CRISPR in one bucket and try to squeeze all that into the AAV world. There are elements of a CRISPR platform that AAV can deliver.”
Dr. Asokan’s lab has also conducted research into RNA and RNA editing, particularly looking at the development of circular RNA (circRNA) and CRISPR-assisted RNA fragment trans-splicing (CRAFT). CircRNA, which is more stable than linear RNA, can potentially improve the durability and efficacy of RNA-based therapies. The CRAFT technique further enhances RNA editing efficiency, offering a possible solution for correcting genetic mutations at the RNA level. Certain genes and RNAs are “too massive to deliver,” explains Dr. Asokan. “If you could just focus on patients having mutations on the left side of the gene or right side of the gene, proceed to deliver half, then go in and correct the RNA, that has profound implications.”
Collaboration Paves the Way Forward
The journey from laboratory research to clinical application is fraught with challenges, particularly in manufacturing. The production of viral vectors, for example, requires highly efficient and consistent methods to ensure therapeutic quality and safety. Both Dr. Asokan and Clive Glover emphasize the need for robust manufacturing processes that can scale to meet clinical demands.
And to get there, collaboration is proving to be a cornerstone of genomic medicine innovation. Dr. Asokan leads the Danaher Beacon for Gene Therapy Innovation, an initiative designed to foster partnerships between academia and industry. The program aims to accelerate translation of research into clinical applications by providing researchers with access to advanced tools and technologies.
For instance, Cytiva supplied a 50-L bioreactor to Dr. Asokan’s lab, which has significantly enhanced its capabilities — enabling scalable production of viral vectors and other therapeutic agents. “We were over the moon with excitement,” says Dr. Asokan of the bioreactor’s installation. “And it didn’t stop there. Engineers came down to help us run it and teach us how to use it, and there’s constant feedback in terms of that discussion.”
And the fact that both sides benefit creates the basis for future collaboration. “We’re an engineering company at Cytiva,” says Glover. “We get into the biology space via cell lines and lipid nanoparticles — but we want to get closer to the biology. Finding somebody who knows about that is incredibly important to us. And there was an equal and opposite need on Dr. Asokan’s side, which is what made this collaboration so fruitful.”
Cytiva continues to work to expand manufacturing capabilities by advancing and expanding their offerings. The acquisition of CEVEC, a company specializing in cell line development, has enabled significant improvements in the yields from cell lines used in viral vector production. Through these developments, Cytiva is helping to reduce the cost of goods and make genomic therapies more accessible. Teamwork between Cytiva scientists and those at the Beacon means productivity is set to ramp up over the coming years.
“We’ve been through similar collaborations in the past,” remarks Glover. “Often, each party is just using the other for some kind of end — they don’t really care what the other party wants out of it. That wasn’t true at all in this case. Both parties clearly recognized what they wanted to learn out of this collaboration; the two were highly complementary.”
The future of genomic medicine lies in the continued integration of diverse therapeutic modalities. The collaboration between academia and industry, as exemplified by the Danaher Beacon initiative, will help to drive innovation forward. By working with Cytiva, genomic medicine pioneers can benefit from the firm’s expertise in multi-modality approaches and strong track record of breaking down bottlenecks to commercialization. Download the whitepaper on this page to find out more.
[1] GlobalData, “The State of the Biopharmaceutical industry: 2024 edition,” page 13.
[2] Ibid., page 24.
