Why is pharmacokinetics (PK) considered a challenge in the development of oligonucleotide drugs?

Question

Accepted Answer

Pharmacokinetics (PK) poses a challenge in the development of oligonucleotide drugs due to several reasons.

Nucleic acid drugs are easy to be degraded by plasma nucleases, its serum stability is poor, and quickly cleared out of the body by the kidneys, so the circulation time of oligonucleotide drugs in the body is short.

In addition, after entering the cell, oligonucleotide drugs tend to accumulate in the nucleus and rather than entering the cytoplasm to play a role.

Therefore, what must be considered in the development of oligonucleotide drugs is that how to keep drugs in the body for a long enough time, and accurately enter the targeted cells to exert therapeutic functions, thus avoiding accidental injury to normal cells to the greatest extent when injecting oligonucleotide drugs into patients.