Sarepta Therapeutics, Inc.

Avi Biopharma, Inc.

Other

M.i.t.

Hong M Moulton

Patrick L Iversen

David A Stein

Michelle H Nelson

Andrew D Kroeker

Ryszard M Kole

Jonathan B Rothbard

David J Hinrichs

Dan V Mourich

Rima McLeod

Kamal El Bissati

Qing Ge

Jianzhu Chen

Ernest J Mui

Bo Shiun Lai

William Witola

Jon D Moulton

An antisense compound for use in treating myotonic dystrophy DM1 or DM2, a method of enhancing antisense targeting to heart and quadricep muscles, and a method for treating DM1 or DM2 in a mammalian subject are disclosed. The oligonucleotide has 8-30 bases, with at least 8 contiguous bases being complementary to the polyCUG or polyCCUG repeats in the 3'UTR region of dystrophia myotonica protein kinase (DMPK) mRNA in DM1 or DM2, respectively. Conjugated to the oligonucleotide is a cell-penetrating peptide having the sequence (RXRR(B/X)R)XB, where R is arginine; B is &#x3b2;-alanine; and each X is &#x2014;C(O)&#x2014;(CH)&#x2014;NH&#x2014;, where n is 4-6. The antisense compound is effective to selectively block the sequestration of muscleblind-like 1 protein (MBNL1) and/or CUGBP, in heart and quadricep muscle in a myotonic dystrophy animal model.

Compound and method for treating myotonic dystrophy

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.

Compositions for enhancing transport of molecules into cells

Pharmaceutical formulations of antisense peptide-conjugated phosphorodiamidate morpholino olgomers and methods of use for treatment of apicomplexan infections are disclosed. The invention is particularly directed to treatment ofinfections.

Conjugate constructs, delivery, and use for treatment of disease

The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Orthomyxoviridae family and in the treatment of a viral infection. The compounds are particularly useful in the treatment of influenza virus infection in a mammal. The antisense antiviral compounds are substantially uncharged morpholino oligonucleotides having 1) a nuclease resistant backbone, 2) 12-40 nucleotide bases, and 3) a targeting sequence of at least 12 bases in length that hybridizes to a target region selected from the following: a) the 5' or 3&#x2032; terminal 25 bases of the negative sense viral RNA segment of Influenzavirus A, Influenzavirus B and Influenzavirus C; b) the terminal 25 bases of the 3&#x2032; terminus of the positive sense cRNA and; and c) the 50 bases surrounding the AUG start codon of an influenza viral mRNA.

Antisense antiviral compound and method for treating influenza viral infection

A method and conjugate for selectively killing antigen-activated T cells are disclosed. The conjugate is composed of a substantially uncharged antisense compound targeted against the human cFLIP protein, and a reverse TAT (rTAT) polypeptide coupled covalently to the antisense compound. The rTAT polypeptide is effective to produce selective uptake of the conjugate into antigen-activated T cells, relative to the uptake of the conjugate into non-activated T cells. The cFLIP antisense compound causes activation induced cell death (AICD) of activated lymphocytes. The method is useful in treating transplantation rejection and autoimmune conditions.

Antisense compound for inducing immunological tolerance

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Corvallis, OR, United States of America

Hong M Moulton