Wave Life Sciences Ltd.

Pachamuthu Kandasamy

Chandra Vargeese

David Charles Donnell Butler

Gopal Reddy Bommineni

Subramanian Marappan

Genliang Lu

Naoki Iwamoto

Sethumadhavan Divakaramenon

Mamoru Shimizu

Christopher P Hencken

Jason Jingxin Zhang

Ilia Korboukh

Vincent Aduda

Stephany Michelle Standley

Mohammed Rowshon Alam

Keith Andrew Bowman

Snehlata Tripathi

Alvaro Andres Lanao

Zhong Zhong

Hailin Yang

Chikdu Shakti Shivalila

Ik-Hyeon Paik

Yuanjing Liu

Jean-Cosme Dodart

Jayakanthan Kumarasamy

Prashant Monian

Ann Fiegen Durbin

Selvi Ramasamy

Nayantara Kothari

Among other things, the present disclosure provides technologies for oligonucleotide preparation, particularly chirally controlled oligonucleotide preparation, which technologies provide greatly improved crude purity and yield, and significantly reduce manufacturing costs.

Technologies for oligonucleotide preparation

The present disclosure, among other things, provides technologies for synthesis, including reagents and methods for stereoselective synthesis. In some embodiments, the present disclosure provides compounds useful as chiral auxiliaries. In some embodiments, the present disclosure provides reagents and methods for oligonucleotide synthesis. In some embodiments, the present disclosure provides reagents and methods for chirally controlled preparation of oligonucleotides. In some embodiments, technologies of the present disclosure are particularly useful for constructing challenging internucleotidic linkages, providing high yields and stereoselectivity.

Compounds, compositions and methods for synthesis

Among other things, the present disclosure provides designed DMD oligonucleotides, compositions, and methods of use thereof. In some embodiments, the present disclosure provides technologies useful for repairing mutant DMD transcripts by skipping exon 51 or exon 53, so that the transcript can be translated into an internally truncated but at least partially functional Dystrophin protein variant. In some embodiments, the present disclosure provides technologies useful for modulating DMD transcript splicing. In some embodiments, provided technologies can alter splicing of a dystrophin (DMD) DMD transcript. In some embodiments, the present disclosure provides methods for treating diseases, such as muscular dystrophy, including but not limited to Duchenne muscular dystrophy, Becker's muscular dystrophy, etc.

Oligonucleotide compositions and methods of use thereof

The present disclosure, among other things, provides technologies for oligonucleotide synthesis. In some embodiments, the present disclosure provides phosphoramidites and methods for synthesis thereof. In some embodiments, provided methods provides higher yields and/or purities. In some embodiments, provided methods remove byproducts without contact with an aqueous solution.

Compositions and methods for phosphoramidite and oligonucleotide synthesis

Among other things, the present disclosure provides oligonucleotides, compositions, and methods thereof. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., knockdown ability, stability, delivery, etc. In some embodiments, the oligonucleotides decrease the expression, activity and/or level of a C9orf72 gene, including but not limited to, one comprising a repeat expansion, or a gene product thereof. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions, for example, in treatment of C9orf72-related disorders.

Oligonucleotide compositions and methods thereof

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Belmont, MA, United States of America

Pachamuthu Kandasamy