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How plasma protein binding can influence biodistribution and activity of antisense oligonucleotides and plasmid DNA?

How plasma protein binding can influence biodistribution and activity of antisense oligonucleotides and plasmid DNA?

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Plasma proteins binding can significantly affect the distribution and clearance of drugs, applicable even to antisense oligonucleotides and plasmid (recombinant) DNA used in treatment of various diseases.

Antisense oligonuclueotides bind to plasma proteins, which slow their metabolism or clearance from the kidneys. As it is seen that most of the oligonucleotides that fall in the size range of 3 to 6 nm or less are easily cleared through renal (kidney) route. Decreased renal clearance increases the half life of the antisense oligonucleotides (about 1 to 3 days, as reported in a study for liver disease).

Secondly, plasma protein binding can serve as a depot (reserviour) for free (unbound) oligonucleotides which can be relased slowly slowly by various elimination processes of the body. This prolongs duration of action of antisense oligonucleotides.

In case of plasmid DNA, plasma protein binding protects the DNA complex from degradation. This increased plasmid (recombinant) DNA uptake by cells / tissues, enhancing therapy efficiency.

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