VectorBuilder and Lir Therapeutics Partner to Develop Scalable, AI-Engineered AAV Capsids for Gene Therapy
VectorBuilder, a global provider of gene delivery technologies, and Lir Therapeutics, a biotechnology company focused on applying artificial intelligence to viral vector engineering, have announced a strategic collaboration aimed at developing next-generation adeno-associated virus (AAV) capsids that combine strong biological performance with improved manufacturability and scalability.
The partnership brings together complementary capabilities from both companies. VectorBuilder contributes expertise in AAV discovery, capsid engineering, process development, and good manufacturing practice (GMP) manufacturing, while Lir Therapeutics will apply its proprietary nAAVigator® artificial intelligence platform and laboratory-based optimization approach.
Together, the companies intend to optimize promising AAV capsids across multiple stages of the development process, beginning with computational engineering and laboratory validation and extending through manufacturing assessment and potential clinical translation.
The collaboration addresses one of the most persistent challenges facing the gene therapy industry: developing viral vectors that not only demonstrate strong biological activity in research studies but can also be manufactured efficiently, consistently, and at commercial scale.
Addressing the Manufacturing Challenge in Gene Therapy
AAV vectors have become one of the most widely explored delivery platforms for gene therapy because of their ability to transport genetic material into targeted cells. However, developing an effective AAV capsid is only one part of the process required to advance a gene therapy toward clinical development.
Many capsids that demonstrate promising tissue targeting, potency, or other biological characteristics during early research can encounter significant challenges during manufacturing. Improvements in one area may sometimes be accompanied by reductions in production yield, product quality, or process consistency.
These manufacturing limitations can become increasingly important as programs progress from discovery into preclinical studies, clinical trials, and eventually commercial production. A vector that performs well in an experimental model may not necessarily be suitable for large-scale manufacturing or practical clinical use.
VectorBuilder and Lir Therapeutics are taking a different approach by incorporating manufacturability into capsid engineering from the earliest stages of development.
Rather than waiting until a promising vector has already been selected to determine whether it can be manufactured effectively, the companies plan to evaluate and optimize manufacturability alongside biological performance.
This integrated strategy is intended to help identify capsids that can meet the requirements of both therapeutic performance and production.
Combining VectorBuilder’s DeepCap Platform With AI
Under the collaboration, Lir Therapeutics will use its nAAVigator® AI platform and laboratory-in-the-loop optimization workflow to enhance selected capsids discovered through VectorBuilder’s DeepCap™ platform.
The approach is not focused solely on designing completely new viral vectors. Instead, the companies plan to start with high-performing capsids that have already demonstrated promising biological characteristics and then engineer those capsids to improve additional properties.
This strategy could allow the companies to preserve useful biological functions while simultaneously addressing manufacturing and translational challenges.
The nAAVigator® platform is designed to combine computational protein engineering with experimental validation. By repeatedly moving between AI-driven design and laboratory testing, the system can generate new data that informs subsequent rounds of engineering.
This iterative process is intended to accelerate optimization and allow researchers to evaluate multiple characteristics of a capsid at the same time.
The collaboration will initially focus on multiple lead capsids and selected therapeutic applications.
Improving Productivity and Product Quality
One of the primary objectives of the partnership is to improve AAV manufacturing productivity and process robustness.
For gene therapy developers, manufacturing efficiency can have a major impact on the feasibility of a therapeutic program. AAV production can require significant resources, and manufacturing processes must generate sufficient quantities of high-quality vector for preclinical and clinical applications.
The partners will therefore evaluate capsids for characteristics such as production yield, full capsid content, product quality, and overall process performance.
Increasing the proportion of full capsids could be particularly valuable because therapeutic activity depends on delivering the desired genetic payload to target cells. Improving production characteristics could potentially reduce manufacturing requirements and help support more efficient development.
By addressing these factors during capsid optimization, VectorBuilder and Lir Therapeutics hope to develop vectors that are better suited for downstream process development and eventual scale-up.
Potentially Lowering Therapeutic Doses
Another major focus of the collaboration is the potential to improve vector potency and reduce the amount of AAV required to achieve a therapeutic effect.
Lower dosing could have several potential advantages for gene therapy development. If a treatment can achieve the desired biological response with less vector, it could reduce manufacturing requirements and potentially improve the overall feasibility of producing the therapy.
Dose reduction may also be relevant to safety and tolerability because high doses of viral vectors can create challenges related to immune responses and other treatment-associated risks.
The companies will therefore explore capsid engineering strategies designed to improve biological performance while maintaining or improving manufacturing characteristics.
Importantly, these objectives will be evaluated through experimental studies rather than relying exclusively on computational predictions.
Enhancing Tissue Specificity
The partnership will also focus on improving tissue targeting and specificity.
AAV capsids determine, in part, how viral vectors interact with cells and tissues in the body. Developing capsids that preferentially reach specific target tissues could improve the efficiency of gene delivery and potentially reduce exposure to tissues that do not need to receive the therapeutic genetic material.
The companies aim to engineer capsids with enhanced tissue specificity while reducing unwanted off-target delivery.
Improved targeting could potentially contribute to more efficient gene transfer and support lower therapeutic doses. It may also help developers design therapies for diseases where precise delivery to a particular organ or cell population is especially important.
Addressing Immune Recognition
Immune recognition is another important consideration in AAV-based gene therapy.
The body’s immune system can recognize viral vector components, potentially affecting treatment effectiveness and limiting the ability to administer therapies repeatedly. The development of capsids with reduced immune recognition could therefore have important implications for the future of gene therapy.
VectorBuilder and Lir Therapeutics intend to incorporate immune-related characteristics into their optimization strategy alongside potency, tissue specificity, and manufacturing performance.
Rather than optimizing one characteristic at a time, the companies are seeking to develop a more comprehensive engineering approach that considers multiple attributes simultaneously.
AI and Experimental Science Working Together
The collaboration reflects the growing role of artificial intelligence in biological research and drug development.
AI-based technologies can analyze large amounts of biological information and identify potential relationships that may be difficult to detect through traditional approaches. In protein engineering, computational models can help researchers predict how changes to a protein sequence could influence its characteristics.
However, computational predictions still require experimental confirmation.
Lir Therapeutics’ laboratory-in-the-loop approach is designed to connect AI-based engineering with real-world laboratory results. Each experimental cycle can generate additional information that feeds back into the computational design process, creating an iterative optimization loop.
By combining this capability with VectorBuilder’s experience in AAV development and manufacturing, the partnership aims to bridge the gap between computational discovery and practical therapeutic development.
Leadership Perspective
Dr. Bruce Lahn, chief scientist of VectorBuilder, emphasized that the gene therapy field requires capsids capable of progressing beyond laboratory discovery and ultimately reaching patients.
According to Lahn, promising vectors can encounter difficulties when programs transition into manufacturing and clinical development. The collaboration is intended to address these challenges earlier by combining VectorBuilder’s expertise in capsid engineering and translational development with Lir Therapeutics’ AI capabilities.
Killian Hanlon, chief executive officer of Lir Therapeutics, similarly highlighted the importance of applying AI to practical biological challenges.
Hanlon said Lir’s goal is to advance viral vector engineering by simultaneously addressing major challenges associated with gene therapy, including dose reduction, tissue targeting, and immune evasion.
The partnership with VectorBuilder is expected to provide an opportunity to demonstrate how AI-guided engineering can further improve capsids that already have strong biological potential.
Toward More Efficient Gene Therapy Development
The collaboration comes at a time when gene therapy developers are increasingly focused on improving not only the biological effectiveness of their products but also the ability to manufacture them efficiently and consistently.
As more gene therapy candidates move toward clinical development, manufacturing considerations are becoming increasingly important. A capsid that requires difficult or inefficient production processes may create challenges for clinical development and future commercialization.
By considering manufacturability during the discovery and engineering process, the companies hope to reduce the likelihood that promising candidates will encounter significant production obstacles later.
The partners plan to evaluate multiple lead capsids across selected therapeutic applications using iterative cycles of AI-guided engineering, laboratory validation, and manufacturing assessment.
Data generated through these activities will be used to support further optimization of VectorBuilder’s capsid portfolio and may also create opportunities for additional therapeutic development partnerships.
Building a More Integrated AAV Development Model
The VectorBuilder-Lir Therapeutics collaboration represents an integrated approach to AAV capsid development in which biological performance, manufacturing, and translational potential are evaluated together.
Traditional vector development can involve sequential stages in which researchers first focus on biological performance and later address manufacturing and scalability. The companies believe that integrating these considerations from the beginning could help accelerate development and improve the likelihood that promising capsids can advance toward clinical applications.
The partnership also demonstrates how AI and experimental science can work together in gene therapy research. Computational tools can help identify and prioritize potential improvements, while laboratory experiments provide the data needed to validate those predictions and guide subsequent optimization.
Ultimately, the goal is to develop AAV capsids that are not only effective in laboratory studies but are also practical for manufacturing, scalable for clinical development, and suitable for eventual therapeutic use.
As the gene therapy industry continues to mature, technologies that combine precise biological targeting with reliable manufacturing are likely to play an increasingly important role. Through their strategic collaboration, VectorBuilder and Lir Therapeutics aim to contribute to this next phase of AAV innovation by developing capsids engineered with the full therapeutic development pathway in mind.
If successful, the approach could help create viral vectors with improved productivity, product quality, tissue specificity, potency, and manufacturing scalability. More broadly, the collaboration highlights a growing shift in gene therapy development toward designing vectors not simply for what they can accomplish in the laboratory, but for what they can realistically deliver throughout the entire journey from discovery to clinical treatment.
About VectorBuilder
VectorBuilder is a global leader in gene delivery technologies. As a trusted partner in thousands of labs and biotech/pharma companies around the world, VectorBuilder is a one-stop shop for the design, development, and optimization of gene delivery solutions from basic research to clinical applications. Its award-winning Vector Studio is a transformative innovation that allows researchers to easily design and order custom vectors online, freeing them from the tedious work of cloning and packaging vectors in the lab.
The global company boasts high-throughput vector production capacity, vast vector and component inventories, one-on-one CRO solutions that include advanced AAV capsid engineering capabilities, and state-of-the-art GMP manufacturing facilities. With leading R&D and CDMO capabilities, the VectorBuilder team strives to provide the most effective gene-delivery solutions and develop innovative tools for life sciences research and genetic medicine.
About Lir Therapeutics
Lir is a techbio company pushing the boundaries of what’s possible with viral vectors. Through the combined development cycle of its nAAVigator® AI pipeline and tightly integrated lab-in-the-loop, Lir is building the next generation of viral vectors for gene therapy and beyond. Starting with AAV, Lir is taking a holistic AI approach editing across the entire virus and is tackling the three biggest challenges facing gene therapy – high doses, off-target effects and pre-existing immunogenicity – all at once. Lir is actively partnering with companies building gene therapies, to develop or enhance viral vectors and create more potent, safer drugs for patients.