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Intracellular delivery is essential for advancing research and clinical applications, yet it presents unique challenges when working with different cell types and biomolecules.

In a recent episode of the Smart Biotech Scientist podcast, David Brühlmann spoke with Armon Sharei, the founder and CEO of Portal Bio, about the future of cell therapy, the hurdles of intracellular delivery, and groundbreaking innovations in drug screening.

Armon’s journey began at MIT, where his initial focus on chemical engineering evolved into a passion for cell engineering. While exploring innovative methods for introducing materials into cells, he discovered a novel mechanism: squeezing cells to temporarily disrupt their membranes, allowing materials to diffuse in.

Armon explained that optimizing delivery parameters - such as pore size and the speed at which cells pass through specialized membranes - can significantly enhance efficiency. "If you've optimized it, one time is enough," he noted. "We can get above 80% delivery and viability pretty easily for most cell types." He emphasized the importance of tailoring pore sizes to specific cell types, such as smaller pores for T cells compared to stem cells. Additionally, the flow speed of cells through the membrane is critical; moving too slowly renders the process ineffective, while moving too quickly can damage the cells.

Tune in to this episode to find out more about:

• Addressing Intracellular Delivery Challenges: Portal Bio’s breakthrough technology uses mechanical deformation to open a cell’s lipid bilayer, allowing materials to diffuse in. This approach overcomes the limitations of traditional methods like electroporation or nanoparticle-mediated delivery, which often depend on molecular charge or risk damaging cells.
• Delivering a Wide Range of Molecules: Portal Bio’s technology is versatile, capable of delivering DNA, RNA, peptides, proteins, and more. Unlike methods tailored to specific molecules, this platform supports diverse applications. For instance, RNA operates in the cytoplasm, making delivery straightforward, while CRISPR complexes require nuclear localization sequences to enable gene editing in the nucleus.
• Streamlining Drug Screening: Portal Bio’s technology also revolutionizes drug screening. Traditional approaches often struggle with impermeable small molecules, leading to lengthy and uncertain drug development processes. By enabling high-throughput screening, Portal Bio accelerates the evaluation of numerous drug candidates, identifying promising options before chemical modifications are necessary.

As bioprocesses grow more advanced, the demand for efficient and versatile intracellular delivery methods becomes increasingly critical. Armon’s insights underscore a transformative shift in the technologies and processes shaping the future of cell therapy and bioprocessing.

Connect with Armon Sharei

LinkedIn: https://www.linkedin.com/in/armonsharei

Portal: https://www.portal.bio

Wondering how to develop cell and gene therapies with peace of mind? Schedule your free assessment to propel your success: https://bruehlmann-consulting.com/assessment

Develop biotherapeutics better, faster, at a fraction of the cost with our 1:1 Strategy Call. Book your call at https://stan.store/SmartBiotech/p/book-a-11-call-with-me-j4vhuo6t

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In part two of our insightful conversation, Dr. Susan Sharfstein builds on our previous discussion of developability assessment to explore how AI is revolutionizing protein manufacturability predictions.

As a Professor of Nanoscale Science and Engineering at the University of Albany, she shares groundbreaking insights from her collaboration with DeepSeq AI, demonstrating how artificial intelligence is transforming our ability to assess and predict protein manufacturability early in development.

Key Takeaways:

• Discover how AI tools are enhancing traditional developability assessments by predicting protein expression and stability before entering the lab
• Learn why integration of experimental validation with AI predictions is crucial for successful manufacturability assessment, and how industry partnerships are making this possible at unprecedented scale
• Understand how the synergy between AI, DNA synthesis capabilities, and robotics is creating a "positive spiral" that will accelerate protein manufacturing innovation

Whether you're involved in candidate selection, process development, or curious about AI's impact on developability assessment, this episode offers valuable insights into the future of protein manufacturing. Plus, Dr. Sharfstein shares invaluable career advice for emerging biotech scientists.

Join us to explore how AI is reshaping developability assessment and learn why this field continues to offer life-changing possibilities for patients worldwide.

Connect with Susan Sharfstein:

LinkedIn: https://www.linkedin.com/in/susan-sharfstein-b7552111/

College of Nanotechnology, Science, and Engineering, University at Albany: https://www.albany.edu/cnse

Next Steps:

Wondering how to develop cell and gene therapies with peace of mind? Schedule your free assessment to propel your success: https://bruehlmann-consulting.com/assessment

Develop biologics better, faster, at a fraction of the cost with our 1:1 Strategy Call. Book your call at https://stan.store/SmartBiotech/p/book-a-11-call-with-me-j4vhuo6t

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In this eye-opening episode, we dive deep into the critical yet often overlooked world of protein manufacturability with Dr. Susan Sharfstein, Professor of Nanoscale Science and Engineering at the University of Albany. As part of the broader developability assessment process, manufacturability evaluation helps determine whether a therapeutic candidate can be successfully produced at commercial scale.

Drawing from her extensive experience in bioprocessing and cell culture technology, Dr. Sharfstein reveals why seemingly promising protein candidates can fail during manufacturing—and how to spot these issues early.

Key Takeaways:

• Discover why efficacy isn't enough: Learn how to evaluate protein candidates beyond clinical performance to ensure manufacturing success
• Master early-stage assessment: Understand the critical parameters that can make or break successful scale-up, from cell line selection to protein folding
• Future-proof your development: Gain insights into how AI is transforming protein manufacturability assessment and what this means for process development

Whether you're selecting protein candidates or optimizing your bioprocess, this episode offers invaluable guidance for making smarter decisions earlier in development. Join us to learn how to bridge the gap between discovery and manufacturing success.

Listen now to transform how you approach protein manufacturability and save valuable time and resources in your development journey.

Connect with Susan Sharfstein:

LinkedIn: https://www.linkedin.com/in/susan-sharfstein-b7552111/

College of Nanotechnology, Science, and Engineering, University at Albany: https://www.albany.edu/cnse

Next Steps:

Wondering how to develop cell and gene therapies with peace of mind? Schedule your free assessment to propel your success: https://bruehlmann-consulting.com/assessment

Develop biologics better, faster, at a fraction of the cost with our 1:1 Strategy Call. Book your call at https://stan.store/SmartBiotech/p/book-a-11-call-with-me-j4vhuo6t