ElevateBio’s Next-Generation Sequencing Core: Meeting the Challenges of Cost, Time and Data Quality with Expertise and Collaboration

Next-generation sequencing (NGS) has accelerated scientific advances and the development of many new therapies by enabling the sequencing of millions of DNA or RNA fragments rapidly and simultaneously. NGS is critical to the development of cell and gene therapies in multiple ways, from determining how process development parameters affect a cell therapy product, to identifying on- and off-target edits of a gene editing system.

ElevateBio recognizes the scientific and economic value of insourcing our NGS capabilities; considering factors such as analysis costs, turnaround times, data quality, and the needs of our partners, clients and R&D teams, which are best served by internal NGS services. Our NGS capabilities can be especially beneficial to startups and smaller biotechs, where making a meaningful capital investment to establish their own NGS laboratories and talent may be challenging.

Here, we discuss the capabilities of our NGS core, the unique advantages we offer to our clients, and our vision for the near future.

Addressing Industry Challenges with an Internal NGS Core 

ElevateBio’s NGS core includes both a wet lab and a dry lab, combining our NGS laboratory with informatics expertise. The laboratory is equipped with sequencing technology platforms and the various materials and kits needed to prepare libraries of DNA or RNA fragments – for sequencing, as requested by our clients. The informatics portion of our group encompasses the computational infrastructure needed to rapidly process, analyze and extract meaningful insights from sequencing data.  

Our NGS core overcomes several industry challenges:

• Turnaround Time: Our core offers turnaround times that are 2-4 weeks faster than external contract research organizations, which is especially meaningful for complex sequencing applications like RNA-seq and Whole Exome Sequencing that may require more time for data analyses.
• Cost: We are continuously optimizing our methods and digital workflows to improve efficiencies and reduce costs.
• Expertise: With decades of combined experience within the NGS team, we understand both the technical and biological aspects of sequencing. This expertise ensures we deliver high-quality, cost-effective data that help clients advance their projects in a meaningful way.
• Collaboration: Our NGS team’s flexibility and collaborative approach are key benefits for our clients. We work closely together starting from designing experiments with the right controls in place to reviewing the data to ensure clarity.

Our Core Applications

ElevateBio’s NGS core can conduct a broad array of sequencing applications, including:

What this means for our customers is access to answers more quickly, faster turnaround times and optimized costs. By continually making efficiency improvements and leveraging our decades of expertise, we can deliver high-quality, cost-effective data, driving meaningful project advancement for customers and their programs.

Evaluating and Optimizing Sequencing Workflows and Technology for Maximum Efficiency

For each of our sequencing applications we’ve developed protocols and optimized the workflow for efficiency, rapid turnaround and high data quality. These optimizations involved side-by-side comparisons of library preparation kits in terms of price, data quality, ease of use and customer support to determine which kit was best for each of our applications. We constantly assess new technology additions to the market and perform comparative testing to identify opportunities to further improve turnaround time, pricing or overall performance.

Our team of experts took the same approach to the more recent launches of novel sequencing platforms: we compare new technologies on the market to our own and assess the potential advantages of upgrading our instrumentation. Staying at the forefront of technological advancements – by thoroughly vetting new innovations and anticipating our client’s needs – is crucial for delivering timely, high-quality data to our partners.

Likewise, we also optimized bioinformatic workflows researching available computational and software tools and performing side-by-side analyses for various applications. Recognizing the importance of streamlined data management early on, we identified the need to focus on our data infrastructure and automate the flow of information from the sequencers into our cloud infrastructure and other data structures. We have a specialized team member focused on meeting this demand as automation is critical for minimizing costs and improving turnaround times.

Next-Generation Sequencing Services are Designed to Support all Cell and Gene Therapy Modalities

Our NGS core supports all the sequencing needs of BaseCamp, our end-to-end process development and cGMP manufacturing business, and Life Edit, our gene editing and R&D technology business, as well as those of our clients.

For Life Edit and partners across the ElevateBio ecosystem, the core’s work has focused primarily on characterization of on- and off-target gene editing. Other projects supporting our internal R&D groups have included single-cell RNA-seq of T cells, to determine if changes in process parameters alter the phenotype of cells; and using RNA-seq, WES, and targeted methylation sequencing to assess whether differentiation protocols for induced pluripotent stem cells (iPSCs) had introduced potentially deleterious alterations to the final, differentiated cells.

We’re continuously innovating and expanding our capabilities to meet the additional needs of client companies. We’re exploring additional applications to help drive initiatives in cell and gene therapies, aiming to offer not only essential assays but also valuable characterization assays as well.

Our Successes Drive the Future of Cell and Gene Therapies

Several measures highlight the impressive progress ElevateBio’s NGS core has made.

1. Faster Turnaround. One key success is the rapid implementation of more efficient automation and library preparation, which has significantly sped up turnaround times for our amplicon sequencing workflow. After testing several optimization strategies to streamline our process and enhance efficiency, we now consistently achieve a throughput of up to 5,000 amplicon libraries with a turnaround time of under 7 days (using Illumina NextSeq 1000/2000).
2. Increased Multiplexing. Another success that we are particularly proud of is how we’ve increased our multiplexing capacity, or the number of individual libraries that can be sequenced in a single run. We’ve gone from 384 last year to 1,536 currently, with plans to reach 2,304 in the coming months (using Illumina NextSeq 1000/2000). This rapid increase was made possible by miniaturizing our reagents and reaction volumes by a factor of ten and incorporating customized indexes or “barcodes” to identify individual libraries in each multi-library run. Multiplexing reduces the cost of analysis per library, and thus increases the overall cost efficiency of our NGS core. 
3. Higher Throughput. By optimizing processes and introducing workflow efficiencies, our throughput can now reach up to 18,000 libraries per month – and will continue to grow, ensuring we stay ahead of the increasing demand for our services.

With cutting-edge technology, expert knowledge, and a collaborative approach, our NGS core provides clients and partners the flexibility, customizability, rapid turnaround times, and high-quality data needed to drive the future of cell and gene therapies.