Nucleic Acids

The nucleic acid component of these therapeutics is the active pharmaceutical ingredient (API) and they often incorporate modified nucleotides that bring greater stability and/or lower immunogenicity, making them critical to the efficacy of these drugs. They are also be conjugated with other biomolecules, encapsulated in lipid nanoparticles (LNPs), or encapsidated in viral vectors to effect targeted delivery. Separating these molecules from synthesis related impurities is critically important for characterization and CMC testing, including impurities analysis and ID.  Mass spectrometry can confirm the ID of these molecules and impurities via mass, and also enables sequence confirmation, and it has the unique ability of being able confirm the ID and location of each modification within the sequence (modification mapping).

Waters offers unique high-performance column chemistries and fit-for-purpose compliance-ready LC-MS workflows that combine unparalleled separations performance with robust and accurate mass analysis to support characterization, monitoring and QC of these nucleic acids.

Featured Technology: ACQUITY Premier Oligonucleotide BEH C18, ACQUITY Premier UPLC systems, BioAccord LC-MS system, XEVO G2-XS QTof, SYNAPT XS QTof with Ion Mobility, MassPREP OST standard, waters_connect

Viral Vectors

Another way nucleic acid sequences are being delivered into cells is to “encapsidate” them in viral vectors that are designed by nature to enter cells and release their genetic payload.  The capsid, or protein-coat of these viral vectors can be varied in ways that provide for targeted delivery.  With these modalities, the native genetic material is replaced with a transgene sequence that gets transcribed and translated into a functional protein once released in the cell.  Viral vectors are being developed for both ex-vivo gene-modified cell therapies (e.g.: Car-T) as well as in-vivo gene therapies (e.g.: Luxturna™ - a intraocular gene therapy from Spark Therapeutics that restores vision in patients with inherited retinal disease). 

The development and characterization of different serotypes and the monitoring of critical quality attributes across development, manufacturing and QC is important to ensuring the safety and efficacy of these large, multi-component drugs.  Key analytical methods include empty/full analysis using anion exchange (AEX) chromatography, PTM (post-translational modification) analyses and confirming viral protein ratios using reversed phase (RP) chromatography and aggregation and titer analyses using size exclusion chromatography (SEC). 

Featured Technology: BioAccord LC-MS System with ACQUITY Premier, ACQUITY BEH C4 300Å column, ACQUITY Premier Peptide BEH C18 300Å column, XBridge Protein BEH450Å SEC column, Empower Software with Auto Blend Plus Technology

Bioprocess Attribute Monitoring

Cell culture media analysis and the direct monitoring of product quality attributes are useful analyses that can accelerate and improve process development whether it be for a viral vector production, clone selection, or propagation of autologous or allogeneic gene modified cells. An automated targeted validation method with Progenesis can increase efficiency.

Featured Technology: BioAccord LC-MS System with ACQUITY Premier, Progenesis QI, UNIFI, MassLynx, AccQTag^TM Ultra, ACQUITY Premier BEH Amide Column, ACQUITY Premier HSS T3 Column

Genomic and Cellular Biology Automation and Preparation

Genomic and Cellular Biology Automation and Preparation
Scalable, consistent identification and quantitation of nucleic acids requires accuracy and traceability built into an automated workflow. These requirements can be achieved using the highly versatile Andrew+ pipetting robot and Pipette+ smart pipetting system, benefitting from the design and execution of protocols for RT-PCR, Next Generation Sequencing (NGS), clonal isolation, and plasmid purification. Moving into to larger complexes, cell preparations for flow cytometry and staining can also be prepared using the same automation system.

Featured Technology: Andrew+, OneLab, BeadTender, Magnet+ www.AndrewAlliance.com