Medical Research Council

Amersham International Plc

Ribotargets Limited

Oxford University Innovation Limited

United Kingdom Research and Innovation

University of York

Ribotargets Holdings Plc

Michael John Gait

Shaun Heaphy

Jonathan Karn

Colin Dingwall

Konrad Misiura

Andrey Alexandrovich Arzumanov

Matthew Wood

Graham McClorey

Ashling Holland

Liz O'Donovan

Andrey Arzumanov

Gareth Hazell

Raquel Manzano

Caroline Godfrey

Richard Raz

Miguel Varela

Ming Jiang

Amer F Saleh

Matthew J A Wood

Corinne Betts

Taeyoung Koo

Gabriela Dimitroval Ivanova

Josephine Anne Milner

Andrei Arzumanov

Peter Jarver

Fazel Shabanpoor

Amer Salah

Matthew Ja Wood

Liz O'DONOVAN

Subhashis Banerjee

The present invention relates to peptides, in particular cell-penetrating peptides, and to conjugates of such cell-penetrating peptides with a therapeutic molecule. The present invention further relates to use of such peptides or conjugates in methods of treatment or as a medicament, especially in the treatment of genetic disorders and in particular muscular dystrophies such as Duchenne muscular dystrophy.

Cell-penetrating peptides

The present invention discloses cell penetrating peptides (CPP or membrane translocating peptide) and their conjugates with cargo molecules. The peptides are useful as drug delivery systems, particularly as delivery vehicles for nucleotide-based therapeutics, such as polynucleotides, oligonucleotides and peptide nucleic acids. A CPPs of the invention provides a balance between good cell entry efficiency and low toxicity and comprises three contiguous domains: the central one being hydrophobic and the flanking ones consisting of arginine and aminohexanoic acid or beta-alanine residues. The hydrophobic domain contains a sequence selected from YQFLI, YRFLI, IQFLI and IRFLI.

Cell-penetrating peptides having a central hydrophobic domain

The present invention discloses cell penetrating peptides and conjugates of a cell penetrating peptide and a cargo molecule.

Cell penetrating peptides

The invention relates to a hybrid interfering RNA molecule comprising a duplex RNA and a single stranded DNA molecule and its use in the ablation of mRNA and in polymerase chain reactions.

Hybrid interfering RNA

A synthetic molecule comprises at least one oligonucleotide comprising an RNA binding sequence or sequences corresponding to the site bound by the HIV protein rev and capable of binding ot rev within cells. The binding sequence or sequences, by binding with rev within cells, can act to cause inhibition of growth of any HIV present in the cells, and so has potential therapeutic use in treatment of patients infected with HIV. The invention also provides an assay for identifying that inhibit rev binding.

Viral growth inhibition

A synthetic molecule comprises at least one oligonucleotide, comprising and RNA binding sequence or sequences corresponding to the site bound by the HIV protein tat and capable of binding to tat within cells. The binding sequence or sequences, by binding tat within cells, can act to cause inhibition of growth of any HIV present in the cells, and so has potential therapeutic use in treatment of patients affected with HIV. The invention also provides an assay for identifying compounds that inhibit tat binding.

Viral (HIV) growth inhibition

Phosphoramidite derivatives of formula (V), ##STR1## wherein X is biotin and Y is a protecting group. There may be a linker arm, of variable length, between X and the rest of the molecule. Examples of the protecting group Y include 4,4'-dimethoxytrityl, trifluoroacetyl and fluorenylmethoxycarbonyl (Fmoc). The phosphoramidite derivatives are useful in single or multiple labelling of synthetic oligonucleotides. Process for the preparation of these phosphoramidite derivatives are also disclosed.

Phosphoramidite derivatives, their preparation and the use thereof in

A synthetic molecule comprising an RNA binding sequence or sequences corresponding to the site bound by the HIV protein tat and capable of binding to tat within cells. The binding sequence or sequences, by binding tat within cells, can act to cause inhibition of growth of any HIV present in the cells, and so has potential therapeutic use in treatment of patients affected with HIV. The invention also provides an assay for identifying compounds that inhibit tat binding.

RNA oligonucleotides that bind HIV tat protein

A synthetic molecule comprises at least one oligonucleotide comprising an RNA binding sequence or sequences corresponding to the site bound by the HIV protein rev and capable of binding to rev within cells. The binding sequence or sequences, by binding rev within cells, can act to cause inhibition of growth of any HIV present in the cells, and so has potential therapeutic use in treatment of patients infected with HIV. The invention also provides an assay for identifying compounds that inhibit rev binding.

Oligonucleotide competitors for binding of HIV RRE to REV protein and

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Cambridge, United Kingdom

Michael John Gait