Gene therapy has long promised to transform the treatment of genetic and acquired diseases by addressing the underlying molecular causes rather than their symptoms. Yet, despite decades of progress in vector design, manufacturing and clinical strategy, delivery remains the central challenge: how to transport fragile nucleic acids safely and efficiently into target cells, while achieving durable expression with minimal toxicity or immune response. Viral vectors, particularly adeno-associated viruses, have led the way, offering high transduction efficiency and clinical precedent. However, their limitations – including restricted payload capacity, immunogenicity and challenges with repeat dosing – have driven intense interest in non-viral delivery systems.
Among these, lipid nanoparticles (LNPs) have emerged as one of the most promising platforms. With clinical validation from mRNA vaccines and a rapidly expanding toolbox of lipid chemistries, LNPs provide a modular, scalable and potentially safer alternative to viral systems. Current work is focused on overcoming the remaining hurdles: achieving tissue- and cell-type specificity, improving endosomal escape and balancing potency with tolerability.
We spoke to Dr. Ying Tam, chief scientific officer at Acuitas Therapeutics, following presentation of exciting clinical data from a landmark case study, published by The New England Journal of Medicine, at the American Society of Gene & Cell Therapy (ASGCT) 2025 Annual Meeting. He discussed what makes their LNP delivery system different, how it’s been used in the clinic and where they hope to go from here.
Karen Steward, PhD (KS):
Senior Scientific Specialist
Technology Networks
Karen Steward holds a PhD in molecular microbiology and evolutionary genetics from the University of Cambridge. She moved into science writing in 2017 after over a decade as a research scientist.
For readers that may be less familiar, can you tell us about LNP delivery systems used in gene therapy and how they compare to other delivery systems?
Ying K. Tam, PhD (YKT):
Chief Scientific Officer
Acuitas Therapeutics
Dr. Ying K. Tam, chief scientific officer of Acuitas Therapeutics, is a globally recognized expert in nanotechnology and immunology. He directs Acuitas’ scientific strategy, partnerships and has authored over 100 peer-reviewed studies. He earned his MSc and PhD in developmental and molecular biology from the University of Waterloo and completed a post-doctoral fellowship in cancer immunotherapy at the BC Cancer Agency. He has held academic roles, including assistant professor at Rush-Presbyterian-St. Luke’s Medical Center in Chicago and adjunct professor at the University of British Columbia.
LNPs are currently one of the most clinically validated delivery technologies for nucleic acid-based therapies, including gene therapy. They act as a vehicle that protects the encapsulated RNA/DNA molecules and delivers them into cells, where the therapeutic effect can be achieved. LNPs are non-viral, which gives them several advantages over viral vectors – such as (1) the ability to be rapidly engineered; (2) high scalability and reproducibility for manufacturing; and (3) a favorable safety and immunogenicity profile. In contrast to viral systems, which trigger strong immune responses and can only be dosed once, LNPs allow redosing. This enables activity to be sustained with additional doses as well as “dosing to effect”.
As a recent example, in the Children’s Hospital of Philadelphia (CHOP) and Perelman School of Medicine at the University of Pennsylvania’s (UPenn’s) personalized CRISPR therapy study, the newborn patient received three separate doses. This ability to redose was critical – it allowed clinicians to escalate the drug amount while confirming safety, and to achieve and sustain the desired therapeutic effect.
KS:
Senior Scientific Specialist
Technology Networks
Karen Steward holds a PhD in molecular microbiology and evolutionary genetics from the University of Cambridge. She moved into science writing in 2017 after over a decade as a research scientist.
What makes Acuitas Therapeutics’ system different from others that might be available?
YKT:
Chief Scientific Officer
Acuitas Therapeutics
Dr. Ying K. Tam, chief scientific officer of Acuitas Therapeutics, is a globally recognized expert in nanotechnology and immunology. He directs Acuitas’ scientific strategy, partnerships and has authored over 100 peer-reviewed studies. He earned his MSc and PhD in developmental and molecular biology from the University of Waterloo and completed a post-doctoral fellowship in cancer immunotherapy at the BC Cancer Agency. He has held academic roles, including assistant professor at Rush-Presbyterian-St. Luke’s Medical Center in Chicago and adjunct professor at the University of British Columbia.
One of the key differentiators of our LNP platform is that it’s built on a “rational design” approach. We have done tremendous amounts of research to understand the individual components of LNPs, and the underlying biology of their mechanics. This allows us to engineer each component of the LNP deliberately – such as ionizable lipids, structural lipids, cholesterol, PEG-lipids and more – and to optimize them for our partners’ specific therapeutic goals. This data-driven approach makes it possible for Acuitas to tailor formulations for a wide range of nucleic acid cargo and to target hard-to-reach cell and tissue types. Our systems are the most clinically validated LNPs, having been used in billions of vaccine doses and to deliver RNA for other therapeutic applications. And we’re applying that deep expertise to advance the delivery of next-generation gene editing and rare disease therapies.
KS:
Senior Scientific Specialist
Technology Networks
Karen Steward holds a PhD in molecular microbiology and evolutionary genetics from the University of Cambridge. She moved into science writing in 2017 after over a decade as a research scientist.
YKT:
Chief Scientific Officer
Acuitas Therapeutics
Dr. Ying K. Tam, chief scientific officer of Acuitas Therapeutics, is a globally recognized expert in nanotechnology and immunology. He directs Acuitas’ scientific strategy, partnerships and has authored over 100 peer-reviewed studies. He earned his MSc and PhD in developmental and molecular biology from the University of Waterloo and completed a post-doctoral fellowship in cancer immunotherapy at the BC Cancer Agency. He has held academic roles, including assistant professor at Rush-Presbyterian-St. Luke’s Medical Center in Chicago and adjunct professor at the University of British Columbia.
We were honored to contribute our LNP delivery technology to this inspiring and important work, which demonstrated the first in vivo gene editing therapy administered to a newborn patient. The treatment used a personalized CRISPR-based system encapsulated in our LNPs to edit the gene responsible for UCD, a rare but serious condition.
I had previously collaborated with Dr. Kiran Musunuru, and when the opportunity arose to treat this infant using an in vivo CRISPR therapy, Dr. Musunuru immediately reached out to request our LNP technology.
What made this effort extraordinary was its speed – just six months from diagnosis to treatment – a timeline made possible only through close collaboration between UPenn, CHOP, Acuitas, Integrated DNA Technologies and Aldevron.
KS:
Senior Scientific Specialist
Technology Networks
Karen Steward holds a PhD in molecular microbiology and evolutionary genetics from the University of Cambridge. She moved into science writing in 2017 after over a decade as a research scientist.
What are some of the key scientific challenges in LNP development to date? Where is Acuitas focusing its current innovation efforts?
YKT:
Chief Scientific Officer
Acuitas Therapeutics
Dr. Ying K. Tam, chief scientific officer of Acuitas Therapeutics, is a globally recognized expert in nanotechnology and immunology. He directs Acuitas’ scientific strategy, partnerships and has authored over 100 peer-reviewed studies. He earned his MSc and PhD in developmental and molecular biology from the University of Waterloo and completed a post-doctoral fellowship in cancer immunotherapy at the BC Cancer Agency. He has held academic roles, including assistant professor at Rush-Presbyterian-St. Luke’s Medical Center in Chicago and adjunct professor at the University of British Columbia.
One of the ongoing challenges with LNPs is achieving an effective tissue-targeting and distribution profile for a given therapeutic goal. Much of the past and current LNP work has focused on liver delivery, which remains a core strength. However, there is a need to deliver to other specific cells or tissues effectively to realize the potential of RNA medicines fully to treat a wide range of diseases. At Acuitas, we’re researching novel engineered LNPs with expanded tissue and cell specificity, capable of delivering beyond the liver – such as our DARPin-conjugated LNPs for delivery to T cells and hematopoietic stem cells.
KS:
Senior Scientific Specialist
Technology Networks
Karen Steward holds a PhD in molecular microbiology and evolutionary genetics from the University of Cambridge. She moved into science writing in 2017 after over a decade as a research scientist.
What do you think the future holds for LNPs in gene editing and healthcare?
YKT:
Chief Scientific Officer
Acuitas Therapeutics
Dr. Ying K. Tam, chief scientific officer of Acuitas Therapeutics, is a globally recognized expert in nanotechnology and immunology. He directs Acuitas’ scientific strategy, partnerships and has authored over 100 peer-reviewed studies. He earned his MSc and PhD in developmental and molecular biology from the University of Waterloo and completed a post-doctoral fellowship in cancer immunotherapy at the BC Cancer Agency. He has held academic roles, including assistant professor at Rush-Presbyterian-St. Luke’s Medical Center in Chicago and adjunct professor at the University of British Columbia.
We strongly believe that LNPs will play a pivotal role in unlocking the full potential of in vivo gene therapy and nucleic acid therapeutics, especially as we continue to see LNPs enable gene editing medicines including CRISPR therapies, which would have been challenging with viral vectors. In the future, we hope to see more precise LNP-based targeting to specific cell types and tissues, with broader applications beyond the liver – including muscle, central nervous system and other hard-to-reach cell types. Ultimately, LNPs will help make gene editing safer, more accessible and applicable to a wider range of diseases.