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US 12,636,372 B2Granted
Immolative cell-penetrating complexes for nucleic acid delivery to the lung
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsTim R. Blake, Paul Wender, Robert Waymouth, Ronald Levy, Ole Haabeth, Rebecca Mcclellan, Adrienne Sallets
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Abstract
There are provided herein, inter alia, complexes, compositions and methods for the delivery of therapeutic, diagnostic and imaging agents, including nucleic acid, into a cell. The complexes, compositions and methods may facilitate complexation, protection, delivery and release of oligonucleotides and polyanionic cargos into lung cells and lung tissue, both in vitro and in vivo.
Claims20
A composition comprising a mixture of a first cationic amphipathic polymer of formula A or B:
- wherein n21 is 10-35 and z2 is 3-20;
- or
- wherein n22 is 10-35 and z2 is 3-20;
- wherein
- R1A is hydrogen, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, —NHC(O)NH2, —NHSO2H, —NHC(O)H, —NHC(O)OH, —NHOH, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and
- R201, R202 are each independently stearyl, oleyl, linoleyl, dodecyl, nonenyl, or cholesterol;
- and
- a second cationic amphipathic polymer of formula C:
- wherein
- n23 is 1-100,
- z6 is 5-15,
- R3A is hydrogen, —CN, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, —NHC(O)NH2, —NHSO2H, —NHC(O)H, —NHC(O)OH, —NHOH, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and
- R203 is stearyl, oleyl, linoleyl, dodecyl, nonenyl, or cholesterol.
10 more elements
Dependencies are inferred from the claim text.