Drug Digest: Engineering LNPs Beyond the Liver for Genetic Medicines

In this episode of BioPharm Drug Digest, Thomas Madden, PhD, CEO of Acuitas Therapeutics, and Dominik Witzigmann, PhD, co-founder and president of NanoVation Therapeutics, discuss how lipid nanoparticle (LNP) engineering is expanding the reach of genetic medicines beyond the liver, tackling one of the field's most persistent delivery challenges to unlock new applications in chronic, rare, and oncologic disease treatment.

Dr Madden explains that most LNP formulations default to hepatic accumulation because the liver's highly fenestrated blood vessels allow particles to extravasate into the interstitial space, unlike most other organs and tissues, which have continuous vascular linings that block access. Dr Witzigmann adds that the liver behaves like the body's filter organ, and conventional LNPs bind blood proteins such as apolipoprotein E (ApoE), which drives their uptake into hepatocytes. This mechanism is useful for liver-directed therapies but is a major barrier to reaching immune cells, stem cells, and lung tissue.

How are passive and active targeting strategies redirecting LNPs to organs beyond the liver?

On passive targeting, Dr Witzigmann describes engineering the LNP itself, through lipid chemistry, lipid ratios, morphology, and surface charge, to extend circulation time and reduce liver clearance, the principle behind NanoVation's long-circulating LNP platform. Dr Madden notes that Acuitas takes a related approach, using long-chain surface polymers to limit ApoE binding and extend circulation, enabling passive accumulation in the spleen, bone marrow, and other select tissues, even as most of the administered dose still reaches the liver.

On active targeting, Dr Madden describes conjugating engineered antibodies to the LNP surface to selectively recognize receptors on target cells, an approach Acuitas is applying to enable in vivo chimeric antigen receptor T cell therapy by directing LNPs to T cells. Dr Witzigmann agrees that ligand-decorated LNPs add valuable specificity but also add manufacturing complexity and cost, and stresses that passive and active targeting are complementary rather than competing strategies.

Explore more BioPharm Drug Digest episodes.

Interviews featuring

Thomas D. Madden, PhD, CEO, Acuitas Therapeutics

Dr Madden obtained his PhD in Biochemistry from the University of London, UK. Having held senior academic and industry positions, Dr Madden founded Acuitas Therapeutics in 2009, guiding the company to a leadership position in lipid nanoparticle (LNP) technology. Acuitas LNP carriers enable Onpattro (Alnylam Pharmaceuticals), the first approved RNA interference therapeutic, and Comirnaty (Pfizer–BioNTech), the first COVID-19 vaccine. Acuitas LNPs also enabled the first patient-specific base editor therapeutics used to successfully treat Baby KJ (CHOP-UPenn). Dr Madden has more than 60 publications, including in Nature, is a Fellow of the American Institute for Medical and Biological Engineering, and is a recipient of the Governor General’s Award for Innovation.

Dominik Witzigmann, PhD, Co-Founder and President, NanoVation Therapeutics

Dr Dominik Witzigmann is an entrepreneurial scientist and 2024 Highly Cited Researcher, recognized among the world’s most influential researchers in nucleic acid delivery. He held research positions at leading institutions (safety/tox, RNAi and cancer, targeted DNA delivery, RNA-based genome editing) and joined Professor Pieter Cullis to focus on extrahepatic RNA delivery. He has held leadership roles in Canada’s NanoMedicines Innovation Network and served on the board of the CRS Gene Delivery and Genome Editing Focus Group. Dominik co-founded NanoVation Therapeutics to advance next-generation LNP technologies for enabling genetic medicines.

Sponsors

This episode of Drug Digest is sponsored by:

• BIOVECTRA
• FUJIFILM Biotechnologies

About BioPharm Drug Digest

Drug Digest is a video series with the BioPharm International® editors, who conduct in-depth interviews with industry experts around the latest research and pipeline developments as well as emerging opportunities, obstacles, and advances in the biopharmaceutical industry related to the manufacturing, distribution, supply, and regulatory compliance of bio/pharmaceutical products.

Upcoming episodes

October/November 2026: The Future of Biopharma Operations and Supply Chains

*No December 2026 episode