siRNA Sequence, Structure, and Modification
- Novel chemistries for improving resistance to enzymatic degradation
- Novel chemistries for reducing immunostimulation
- Enhanced RISC incorporation
- Long-term chemical stability
- Improved target specificity
Approaches to Molecular Targeting of siRNA
- Targeting using antibodies, peptides, or small molecules
- Specific for disease-relevant cell types
- Suitable for nanoparticle or liposome delivery
Assays for siRNA Intracellular Functions
- Assays for siRNA endosomal escape
- Biochemical assays for strand selection, RISC incorporation,
catalytic efficiency
- Assays for clinical biodistribution
- Cell-based assays to measure Toll receptor activation
Validated siRNA Targets
- Demonstrated reduction in mRNA and protein levels in animals
- Reductions have expected effect on disease phenotype
miRNA
- Novel chemistries to create antagomirs
- Demonstrated reduction of miRNA levels in animals, with evidence that reductions have expected effects on mRNA levels and/or disease phenotype
- Demonstrated delivery of miRNA in animals, with evidence that increases in miRNA have expected effects on mRNA levels and/or disease phenotype
RNA Manufacturing
- Advancements in large-scale production of modified siRNA
- Improved processes for increased quality, efficiency, and reduced COG
- Novel chemistries
- Universal linker based solid support for production of siRNAs
- Robust LC-MS method for determination of impurity profile of phosphoramidite raw materials and oligonucleotides (siRNAs)
Information Technology
- Registration and tracking of information related to complex multi-component biologics
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