Delivery of Macromolecules: Overcoming Biological Barriers to Therapeutic Success
Effective delivery remains one of the biggest hurdles in turning macromolecular therapies - including oligonucleotides, RNA, peptides, and protein‑based systems - into clinically meaningful medicines. This track explores breakthrough receptor‑targeting strategies, advanced lipid nanoparticles, peptide conjugates, and organ‑selective platforms that improve biodistribution, target specificity, and therapeutic efficacy. Are you ready to master the delivery challenges shaping the next generation of macromolecule medicines?
What are the key topics for this track?
CNS Delivery: Crossing the Blood-Brain Barrier
Efficient delivery to the brain remains a major bottleneck for treating neurological diseases. Targeted approaches leveraging the transferrin receptor (TfR) or IGF1R receptors, bispecific brain shuttles, and antibody–oligonucleotide conjugates are enabling robust CNS distribution at low doses.
Why this matters now:
Neurological diseases like Alzheimer’s, Parkinson’s, and Duchenne muscular dystrophy require precise delivery to deep brain regions, making CNS-targeting platforms essential for therapeutic success.
Key Session to Attend:
Unlocking the Therapeutic Potential of Oligonucleotides for CNS Disorders Through Targeted Delivery - Learn how TfR1-targeting oligonucleotide platforms achieve widespread CNS distribution and functional improvements in preclinical models.
Extrahepatic & Organ-Selective Delivery
Targeted delivery beyond the liver allows oligonucleotide and RNA therapies to reach tissues such as muscle, adipose, and kidney. Platforms like SORT LNPs, LEAD™, and STRIKE™ are demonstrating potent, selective, and safe gene silencing in specific organs.
Why this matters now:
Expanding tissue coverage addresses previously untreatable conditions, including obesity, metabolic diseases, and renal disorders, unlocking the full therapeutic potential of RNAi medicines.
Key Session to Attend:
The Strike Platform Enables Kidney-Selective Gene Silencing - Explore ligand-conjugated siRNA strategies achieving >70% kidney-specific knockdown with prolonged effects in preclinical models.
Peptide and Protein-based Delivery Systems
Peptides, mini-proteins, and engineered Fc domains enable receptor-mediated transport of RNA and oligonucleotide payloads to target tissues. Deep learning and high-throughput evolution platforms are accelerating discovery of ligands for both CNS and peripheral delivery.
Why this matters now:
Peptide and protein delivery systems provide modular, versatile solutions to overcome cell- and tissue-specific barriers, improving efficiency, safety, and clinical translatability.
Key Session to Attend:
Discovery and Translation of Extrahepatic Peptides for Oligonucleotide Delivery - Learn how directed evolution and machine-guided design identify functional motifs for precise tissue targeting.
Lipid Nanoparticles & RNA Delivery Platforms
Next-generation LNPs, including SORT and targeted CAR T platforms, are expanding delivery of mRNA and siRNA to systemic and extrahepatic tissues. These approaches combine advanced chemistry, ligand modification, and targeted payload design.
Why this matters now:
Efficient, scalable, and safe delivery vehicles are critical for clinical translation of RNA therapeutics, particularly for systemic or immune-modulating applications.
Key Session to Attend:
In Vivo Generation of Functional CAR T Cells via Targeted Non-Viral Lipid Nanoparticles - See how targeted LNPs generate transient CAR T cells in NHPs, achieving potent immune modulation without lymphodepletion.
Who's Speaking on the Delivery of Macromolecules track?
FAQs
What makes CNS delivery of oligonucleotides so challenging?
The blood-brain barrier restricts access of most large molecules. Innovative strategies using receptor-targeted antibodies, bispecific brain shuttles, and peptide conjugates are now enabling systemic oligonucleotides to reach deep brain regions efficiently.
Can RNA and oligonucleotide therapies be delivered outside the liver?
Yes. Platforms such as SORT LNPs, LEAD™, and STRIKE™ demonstrate selective delivery to muscle, adipose, and kidney, opening new possibilities for metabolic, renal, and systemic diseases.
How do peptide and protein-based delivery systems work?
Peptides, mini-proteins, and engineered Fc domains bind specific cell-surface receptors, mediating endocytosis and tissue-specific uptake. Machine learning and high-throughput evolution are accelerating the discovery of functional ligands.
Are these delivery platforms ready for clinical translation?
Many are. TV platforms, TfR-targeting brain shuttles, and STRIKE™ kidney-targeted siRNAs have preclinical and early clinical validation, with several programs already progressing into human studies.
How do next-gen LNPs differ from traditional lipid nanoparticles?
Next-gen LNPs, including SORT and targeted CAR T platforms, are optimized for tissue-specific delivery, ligand conjugation, and immune compatibility, allowing in vivo generation of functional RNA therapies beyond liver-targeted applications.
What are the main challenges in delivering oligonucleotides and RNA therapeutics?
Efficiently transporting large molecules to specific tissues, especially the brain, kidney, or muscle, remains a major barrier. Safety, tissue specificity, and maintaining functional activity are key considerations.
This track specifically highlights:
Transferrin receptor (TfR) and IGF1R-targeting strategies to enable CNS and peripheral tissue delivery.
Ligand-modified LNPs, peptide conjugates, and bispecific “brain shuttles” to improve uptake and reduce off-target exposure.
Organ-selective platforms like STRIKE™ (kidney) and LEAD™ (adipose/muscle) for tissue-specific gene silencing.
Preclinical and translational demonstrations in rodents and non-human primates showing robust delivery and therapeutic effects.