Discussing Trends in New Analtyical Tools for RNA (AAPS PharmSci 360)

Editor's note: this interview was originally published on PharmTech.com.

Sitting with the Pharmaceutical Technology Group at AAPS PharmSci 360,Bala Addepalli, PhD, Director, R&D New Modalities Portfolio, Waters Corporation, spoke on major trends in the development of new analytical tools for RNA characterization. DNA sequencing technologies, Addepalli pointed out, have pushed the sequencing of RNA as well.

“Those technologies are referred to as next-generation sequencing; the problem with the next-generation sequencing is that it's an indirect sequencing method,” Addepalli stated. “That means the RNA is converted into DNA, so … you would lose some information during this conversion process. We need to do direct sequencing of RNA, [and] that's what people have realized while analyzing these RNA drugs and RNA therapeutics.”

“There are a lot of ambiguities in the sequence interpretation and data accuracy, so that's where … new tools and software can come into the picture,” Addepalli also said. “Having … enzymes that would improve the sequence coverage, and … a simple sample preparation method can help reveal the full information. That's where the trends are being focused, on analytical characterization [and on] how to simplify the process of RNA characterization through direct methods. [Those are] the major trend[s] that's been going on currently.”

Addepalli also highlighted some key points from his presentation at AAPS PharmSci 360 on Oligo Mapping of Large RNA Therapeutics by Novel Enzyme Specificities, in which he talked about enzymes, "[their] properties and their applications in characteriz[ing] large RNA therapeutic drugs, [such as] single guide RNA that is used in genome editing, and mRNA [messenger RNA] as part of the LNPs [lipid nanoparticles] that are used for vaccinations, or cancer therapies, or protein replacements,” he said.

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Attendees can visit Waters Corp. at Booth #2438 at AAPS PharmSci 360, which is being held on Oct. 20–23, 2024 in Salt Lake City, UT.

About the speaker

Bala Addepalli, PhD, Director, R&D New Modalities Portfolio, Waters Corporation

Bala Addepalli, Bala_Addepalli@waters.com, is currently working as director of the Evaluations and Application Science Team under New Modalities (Cell and Gene Therapy product analysis) portfolio of Waters Corporation. His interests include development of simpler but efficient approaches for cell and gene therapy products such as messenger RNA (mRNA), lipid nanoparticle (LNP), and adeno-associated virus (AAV) analysis through liquid chromatography coupled with light scattering and mass spectrometry-based detection techniques.Prior to joining Waters, Addepalli developed novel enzymes and analytical methods for characterization of cellular RNA and modified oligonucleotides through mass spectrometry at University of Cincinnati. Before that he worked on RNA processing events including mRNA polyadenylation at University of Kentucky, and viral RNA characterization through mRNA translation for his graduate studies at Indian Agricultural Research Institute, New Delhi, India. Bala has authoredover 60 publications in peer-reviewed scientific journals and has delivered oral presentations at scientific meetings.