Compositions for enhancing transport of molecules into cells
AssigneeSarepta Therapeutics, Inc.
InventorsPatrick L. Iversen, Hong M. Moulton, Michelle H. Nelson, David A. Stein, Andrew D. Kroeker
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Abstract
Compositions and methods for enhancing delivery of molecules, e.g. biological agents, into cells are described. The composition is a conjugate of the biological agent, preferably a nucleic acid analog having a substantially uncharged backbone, covalently linked to a peptide transporter moiety as described. Conjugation of the peptide transporter to a substantially uncharged nucleic acid analog, such as a morpholino oligomer, is also shown to enhance binding of the oligomer to its target sequence and enhance antisense activity.
Claims18
A peptide-oligomer analog conjugate comprising a carrier peptide covalently linked to a nucleic acid analog, the nucleic acid analog comprising a substantially uncharged backbone and a targeting base sequence, and the carrier peptide consisting of ten to fifteen subunits selected from X and Y subunits, including eight to thirteen X subunits, two to four Y subunits, at least one linker subunit linking the nucleic acid analogue to the peptide carboxy terminus, wherein:
- (a) each X subunit is independently an amino acid subunit comprising a side chain of the structure R1N═C(NH2)R2, where R1 is H or R;
- R2 is R, NH2, NHR, or NR2, where each R is independently lower alkyl or lower alkenyl and optionally comprises oxygen or nitrogen,
- or R1 and R2 may together form a ring;
- and wherein the side chain is linked to the amino acid via R1 or R2;
- and
- (b) each Y subunit is independently a hydrophobic amino acid, and
- wherein each linker subunit comprises the formula —C(O)—(CH2)n—NH, wherein n is an integer from 2 to 7.
Dependencies are inferred from the claim text.