Addressing the challenge of screening DNA-LNP formulations for targeting the brain

Live30 webinars are thirty-minute presentations designed to update you on the latest innovations, applications, and data in a fast yet interactive format.

Developing hundreds of LNP formulations rapidly for in vitro screening is a significant challenge, particularly when considering multiplexing LNPs using barcoding strategies to increase throughput.

Furthermore, transitioning LNP production processes from screening to process development is often fraught with obstacles. Equipment changes result in resource wastage and demanding process re-validation, making the transition to the next stage a complex undertaking.

In this webinar, Razieh Karamzadeh will present data from experiments conducted at Karolinska Institute using Unchained Labs’ Sunscreen and Sunshine systems for production of DNA-LNPs for in vitro screening, then scaling-up selected LNPs for in vivo studies.

Razieh will demonstrate how she reproducibly created DNA-LNPs for in vitro 2D and 3D culture screening and in vivo testing. Combining formulation screening with 3D culture, this approach addressed some of the challenges of extra-hepatic delivery.

Razieh will also demonstrate how the use of both systems simplified the process of testing hundreds of formulations, followed by early scale-up for more comprehensive testing. This streamlined approach significantly accelerated the transition from large multiplexed LNP screens to process development of selected formulations, and can ultimately facilitate GMP production by maintaining consistent pumping and mixing technologies.

Key Takeaways:

• The challenges of targeted delivery of LNPs
• The key benefit of high-throughput screening for improving extra-hepatic delivery
• The benefit of consistent particle production at different volume scales

Razieh Karamzadeh

Post-doc researcher, Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics at Karolinska Institutet

Razieh got her BS and MA in molecular cell biology and PhD in biophysics. She started her post-doc in 2019 at the Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics. Her research focus in her post-doc has been designing, multiplexing & developing high-throughput screening (HTS) for DNA-lipid nanoparticles (DNA-LNPs) using automated microfluidic systems and establishing 2D and 3D in vitro and ex vivo culture models for LNP screening targeting the brain.

Benjamin Knappett

Market Manager, LNPs at Unchained Labs

Ben Knappett received his MChem degree from Durham University and completed a PhD in nanoparticle synthesis and characterization at the University of Cambridge. Ben started working for Particle Works in 2016, developing nanoparticle and microparticle products using microfluidics technology, which covered a wide range of material types. Ben moved to the position as the Head of Science and Applications when the Particle Works brand was relaunched in 2021 as a provider of automated nanoparticle synthesis platforms. Following the acquisition of Particle Works to Unchained Labs, Ben undertakes the role of Product Manager – LNP Solutions, focusing on the delivery of automated, high-throughput solutions for LNP encapsulation in drug delivery, vaccines, gene therapy.