Cell & Gene Therapy Products 2022

Genome editing is rapidly progressing into a new treatment paradigm for a wide range of human diseases. Its ability to permanently modify the target sequence allows the potential to achieve long-lasting or curative effects. Like every innovation, the clinical use of genome editing technologies comes with its own challenges.
Speakers will address the most critical aspects to consider in the design and control of the different genome editing tools to improve specificity and avoid genotoxicities. As important differences are expected for in vivo vs ex vivo applications, both approaches will be covered.
Phillip Ramsey will provide an overview of genome editing platforms, on-target safety evaluation, off- target identification, and provide recommendations on how to assess these potential risks and how to minimize these risks from a CMC perspective.
Jonathan Phillips will present an overview of therapeutic CRISPR/Cas9 genome editing, using NTLA-2001 as an example with a focus on the assessment of mutagenicity (off-target) and chromosomal structural integrity, followed by a discussion of genetic safety considerations and approaches.
Cicera Lazarotto will discuss the risks of inadvertently introducing oncogenic off-target mutations and present sensitive analytical methods, such as GUIDE-seq, CHANGE-seq, and Digenome-seq, for defining the genome-wide activity of genome editors, to better understand the features that drive the genome-wide activity of engineered nucleases, and the frequency and location of resulting off-target mutations.

Modern medicines call for modern technologies. Revolutionary cell and gene therapies offer significant promise to treat life-threatening diseases. Getting therapies to market quickly and efficiently requires accurate testing of critical quality attributes, including accurate viral vector analysis.

In this technical seminar, you'll learn how a variety of innovative analytical tools from Bio-Techne can help give you the automation and scalability you need on your road to discovery, along with consistent, high-quality data across labs and project phases. You'll discover how these next-generation analytical solutions are designed to easily fit into your current workflows and adapt to your changing needs.

Imagine that you just completed a manufacturing run for a mission critical gene therapy vector. All of your release testing is underway, and you are days away from releasing your product. Per regulatory guidelines, identity testing is performed to confirm the vector sequence is as expected. In order to obtain the full sequence of the vector, Next Generation Sequencing is used. The identity test results come back and to your dismay, the sequencing data reveals several unexpected sequence variants in the vector preparation! An insertion with a frequency of 7%, several substitutions with frequencies ranging from 2-8%, and a deletion with a frequency of 10%. The unexpected results lead to an investigation causing the release of the product to be significantly delayed

The situation described above is not hypothetical, and happens more that you think, costing valuable time and resources and introducing significant delays. Avoiding this situation is actually quite easy with an appropriate risk mitigation testing strategy at critical parts of the manufacturing process.

Viral-based vectors are commonly manufactured through the transfection of a series of plasmids into production cells. Plasmids used to produce vectors are manufactured to GMP compliance including a confirmation of the correct sequence. Adequate identification of low-level variants with an appropriately sensitive method is critical in ensuring the quality of the final product. Investigatory testing has shown that sequence variants present in starting materials (e.g., plasmids) are very likely to make their way to the final product. A risk-based testing strategy, in the context of identity, for viral vector manufacturing will be presented, focusing on key testing points. Next generation sequencing assays for identity and variant detection will be highlighted due to their extremely sensitive nature when compared to traditional approaches. Regulatory requirements in regard to identity testing will also be presented and discussed.