Chemical Industry

A French biotechnology SME specialized in glycochemistry and therapeutic targeting has developed a platform of synthetic ligands designed to address one of the major limitations of lipid nanoparticle (LNP) drug delivery: the difficulty of achieving efficient delivery to tissues beyond the liver. LNP-based delivery systems have become a key technology for the administration of therapeutic payloads such as antisense oligonucleotides, nucleic acids, gene-editing components and other advanced therapeutics. While these systems can protect cargo from biological degradation and facilitate intracellular delivery, their natural biodistribution results predominantly in liver accumulation, restricting their use for extrahepatic indications. Various approaches have been investigated to overcome this limitation, including modifications of lipid composition and strategies relying on protein corona formation. However, these approaches have shown limited ability to achieve efficient and controlled delivery to non-hepatic tissues. To address this challenge, the SME has developed patented ligands targeting the mannose 6-phosphate receptor (M6PR), a receptor expressed on a broad range of cell types. When conjugated to lipid nanoparticles, these ligands promote receptor-mediated uptake and facilitate intracellular trafficking. This approach enables enhanced delivery to tissues such as skeletal muscle and tumour tissues, including prostate cancer. The ligands are synthetic, hydrosoluble and highly stable in biological fluids. They can be grafted onto nanoparticles through a rapid, reproducible and metal-free click chemistry process. No specific immune response has been observed following repeated intravenous administrations. The ligands are currently available at pre-GMP scale. The technology is particularly relevant for developers of LNP-based therapeutics, antisense oligonucleotide delivery systems, gene-editing platforms and other advanced therapeutic modalities requiring extrahepatic biodistribution. Potential application areas include oncology, muscular disorders and age-related diseases. The SME possesses the expertise and infrastructure required for ligand conjugation, physicochemical characterization and in vitro evaluation. Under research and development cooperation agreements, partners will contribute their nanoparticle platforms, therapeutic payloads and development expertise, while the SME will provide the targeting ligands and associated know-how. Joint evaluation, optimization and validation of targeted nanoparticle formulations are envisaged. Alternatively, ligands may be supplied to partners for independent conjugation and assessment within collaborative development projects. Advantages and innovations: The technology combines a patented receptor-targeting strategy with practical implementation features that facilitate integration into existing nanoparticle development programmes. Key advantages include: • Targeting of the mannose 6-phosphate receptor, which is expressed on multiple cell types and offers broader tissue accessibility than liver-specific receptors such as the asialoglycoprotein receptor (ASGPR). • Enhanced biodistribution beyond the liver, enabling delivery to tissues including skeletal muscle and tumour tissues. • Receptor-mediated intracellular uptake of large nanoparticle cargoes measuring hundreds of nanometres. • Exploitation of the natural role of M6PR in endosomal trafficking, supporting intracellular delivery pathways relevant for nucleic acid therapeutics. • Rapid receptor recycling, with receptor return to the cell surface occurring in less than 15 minutes. • Hydrosoluble ligands that can improve formulation properties. • High stability in blood due to resistance to phosphatase degradation, unlike the natural mannose 6-phosphate ligand. • Simple one-step, metal-free click chemistry conjugation process that is highly reproducible and compatible with nanoparticle engineering. • Small molecular size and absence of observed specific immune responses following repeated intravenous administration. • Availability at pre-GMP scale, facilitating progression toward translational and preclinical development. Compared with conventional liver-targeting approaches, the technology offers a practical route to expanding the therapeutic scope of lipid nanoparticle platforms for extrahepatic diseases, particularly in oncology and muscular disorders. Expected role of a partner: The company is seeking pharmaceutical companies, biotechnology companies, research and technology organisations, and academic research institutes active in the fields of nanomedicine, lipid nanoparticle (LNP) development, nucleic acid therapeutics, antisense oligonucleotides, gene-editing technologies, oncology, muscular disorders and age-related diseases. Partners should be developing therapeutic candidates, delivery platforms or nanoparticle-based products that would benefit from enhanced delivery beyond the liver. They are expected to contribute therapeutic payloads, nanoparticle formulations and development programmes suitable for evaluating the targeting technology. Desired expertise includes: • Lipid nanoparticle design, formulation and manufacturing; • Antisense oligonucleotide delivery systems; • Gene-editing delivery platforms; • Nanoparticle characterization and optimization; • Preclinical evaluation, including biodistribution and efficacy studies; • Development of therapeutics targeting oncology, muscular disorders or other extrahepatic indications. • Experience in advancing innovative drug delivery systems toward clinical development would be considered an asset. Cooperation will be implemented through joint research and development activities aimed at integrating and evaluating the ligand technology within the partner’s nanoparticle platform or therapeutic programme. The French SME will provide access to its patented mannose 6-phosphate receptor-targeting ligands, together with expertise in chemical conjugation, characterization and in vitro assessment. Partners will contribute their therapeutic candidates, nanoparticle systems and application-specific development expertise. Depending on the project structure, the SME may perform ligand conjugation and preliminary evaluation activities or alternatively supply the ligands to the partner for in-house conjugation, testing and validation. The collaboration will focus on optimizing extrahepatic delivery, assessing biological performance and generating data to support further preclinical and clinical development.