Several classes of pharmacologically interesting molecules contain phosphate group(s) that prevent efficient transport into cells. Beyond small molecule nucleotides, oligonucleotide therapeutics (including siRNA, miRNA, and antisense oligonucleotides, among others) contain numerous problematic phosphate groups. Furthermore, phosphate-containing molecules are prone to extracellular degradation by nucleases or clearance through the kidney.
Although the phosphate group(s) contribute to poor drug-like properties, they are generally required for biologic activity. Thus, the therapeutic potential of nucleotides and oligonucleotides requires new technical solutions to realize their full potential.
Requisite features of an ideal delivery solution include biocompatibility, protection from nucleases, controlled distribution (both persistence and location), full activity and safety.
Solstice has developed unique and proprietary chemical modifications of phosphate groups in nucleotides and oligonucleotides that not only prevent non-productive degradation or elimination, but importantly maintain full biological function. These highly versatile modifications provide handles to functionalize the molecules and enhance key performance characteristics such as potency, stability, and ease of synthesis.