The Royal Institution for the Advancement of Learning/mcgill University

Mcgill University

Wisconsin Alumni Research Foundation

The Hong Kong Polytechnic University

Paladin Labs Inc.

Other

Southern Illinois University

Masad Jose Damha

Glen Deleavey

Tak-Hang Chan

Michael A Parniak

Robert Alexander Donga

Franco Cerrina

Marvin P Wickens

Jeremy Lackey

Mallikarjuna Reddy Nandyala

Jonathan K Watts

Kevin Petrecca

Matthew Hassler

Debbie Mitra

Mark Somoza

Kyung-Lyum Min

Xun He

Daniel Timothy O'Reilly

Chun-Nam Lok

Elise Malek-Adamian

Zachery Kartje

Ekaterina Vlazovkina

Rami N Hannoush

Sandra Carriero

Keith Gagnon

Maryam Habibian

Weishi Miao

Ekaterina Viazovkina

The present disclosure provides CRISPR/Cas9 ribonucleoprotein compositions comprising chemically modified CRISPR RNA (crRNA) guide and trans-acting CRISPR RNA (tracrRNA) components. Methods of using the disclosed CRISPR/Cas9 ribonucleoprotein compositions are also provided.

Tuning CRISPR/Cas9 activity with chemically modified nucleotide substitutions

The invention relates to the chemical synthesis of oligonucleotides, e.g., oligoribonucleotides. In another aspect, the invention relates to compounds of formula (II): processes for making these compounds, and the use thereof in the chemical synthesis of oligonucleotides, e.g., oligoribonucleotides. The invention also relates to methods of synthesis of oligomers, including but not limited to oligopeptides, oligosaccharides and oligonucleotides, particularly oligoribonucleotides and also oligodeoxyribonucleotides, in solution systems, and ionic tag linkers for use in methods provided herein.

Ionic tags for synthesis of oligoribonucleotides

The present invention is directed to RNA monomers comprising O-acetal levulinyl protecting groups at the 2' and/or the 5&#x2032;-hydroxy functionalities of the ribose moiety. Said monomers may be incorporated into oligoribonucleotides or RNA polynucleotides. Furthermore, the invention is directed to methods for the synthesis of said RNA monomers, oligoribonucleotides and RNA polynucleotides, as well as methods for their deprotection and methods for the use of said compounds and compositions comprising said compounds. In particular, such compounds and compositions comprising them are used in methods for light-directed synthesis of RNA microarrays.

RNA monomers containing 0-acetal levulinyl ester groups and their use in RNA microarrays

The present invention relates to ionic liquids for use in chemical applications and capable of serving the dual function of solvent and liquid support. The ionic liquid lends itself to a method of synthesizing oligomers selected from the group consisting of oligopeptides, oligosaccharides and oligonucleotides, comprising contacting a first monomer unit with an ionic liquid at reaction conditions to provide an ionic liquid bound monomer unit; and contacting the ionic liquid bound monomer unit with at least one further monomer unit at reaction conditions to provide an ionic liquid bound oligomer comprising from 2 to 30 monomer units. The method lends itself to large scale manufacture of oligopeptides, oligosaccharides and oligonucleotides.

Ionic liquid supported synthesis

The invention relates to the chemical synthesis of oligonucleotides, e.g., oligoribonucleotides. In another aspect, the invention relates to compounds of formula (II) processes for making these compounds, and the use thereof in the chemical synthesis of oligonucleotides, e.g., oligoribonucleotides. The invention also relates to methods of synthesis of oligomers, including but not limited to oligopeptides, oligosaccharides and oligonucleotides, particularly oligoribonucleotides and also oligodeoxyribonucleotides, in solution systems, and ionic tag linkers for use in methods provided herein.

The invention relates to oligonucleotides having alternating segments of sugar-modified nucleosides and 2'-deoxynucleosides, and uses thereof. The invention further related to oligonucleotides having alternating segments of sugar-modified nucleotides and 2&#x2032;-deoxynucleotides, and uses thereof. Such uses include the preparation of antisense oligonucleotides and their use for the prevention or depletion of function of a target nucleic acid of interest, such as an RNA, in a system. Accordingly, and oligonucleotide of the invention is useful for therapeutic, analytical and diagnostic methods and uses, as well as component of compositions and commercial packages corresponding to such methods and uses.

Oligonucleotides comprising alternating segments and uses thereof

Novel oligonucleotide pairs which can form a duplex comprising one or more DNA-like nucleotides (e.g., 2'-substituted arabinonucleotides (ANA)); in combination with one or more RNA-like nucleotides (e.g., 2&#x2032;-substituted ribonucleotides (RNA) and/or locked nucleic acid nucleotides (LNA)), are disclosed. The use of such oligonucleotide duplexes, such as for silencing the expression of a nucleic acid or gene of interest using small interfering RNA (siRNA) technologies, is also disclosed.

Oligonucleotide duplexes comprising DNA-like and RNA-like nucleotides and uses thereof

The present invention relates to novel compositions and therapeutic methods for the treatment of cancer, in particular malignant glioma. The compositions include antisense oligonucleotides or RNAs or vectors encoding them which reduce expression of downregulated in renal cell carcinoma (DRR) in tumor cells, and inhibit malignant glioma cell invasion.

Method for reducing expression of downregulated in renal cell carcinoma in malignant gliomas

RNA monomers containing O-acetal levulinyl ester groups and their use in RNA microarrays

Novel oligonucleotide pairs which can form a duplex comprising one or more DNA-like nucleotides (e.g., 2'-sub-stituted arabinonucleotides (ANA)); in combination with one or more RNA-like nucleotides (e.g., 2&#x2032;-substituted ribonucleotides (RNA) and/or locked nucleic acid nucleotides (LNA)), are disclosed. The use of such oligonucleotide duplexes, such as for silencing the expression of a nucleic acid or gene of interest using small interfering RNA (siRNA) technologies, is also disclosed.

The invention relates to oligonucleosides having alternating segments of sugar-modified nucleosides and 2'-deoxynucleosides, and uses thereof. The invention further relates to oligonucleotides having alternating segments of sugar-modified nucleotides and 2&#x2032;-deoxynucleotides, and uses thereof. Such uses include the preparation of antisense oligonucleotides and their use for the prevention or depletion of function of a target nucleic acid of interest, such as an RNA, in a system. Accordingly, an oligonucleotide of the invention is useful for therapeutic, analytical and diagnostic methods and uses, as well as a component of compositions and commercial packages corresponding to such methods and uses.

The present invention relates to novel oligonucleotide chimera used as therapeutic agents to selectively prevent gene transcription and expression in a sequence-specific manner. In particular, this invention is directed to the selective inhibition of protein biosynthesis via antisense strategy using oligonucleotides constructed from arabinonucleotide or modified arabinonucleotide residues, flanking a series of deoxyribose nucleotide residues of variable length. Particularly this invention relates to the use of antisense oligonucleotides constructed from arabinonucleotide or modified arabinonucleotide residues, flanking a series of deoxyribose nucleotide residues of variable length, to hybridize to complementary RNA such as cellular messenger RNA, viral RNA, etc. More particularly this invention relates to the use of antisense oligonucleotides constructed from arabinonucleotide or modified arabinonucleotide residues, flanking a series of deoxyribose nucleotide residues of variable length, to hybridize to and induce cleavage of (via RNaseH activation) the complementary RNA.

Chimeric antisense oligonucleotides of arabinofuranose analogue and deoxyribose nucleotides

The invention relates to oligonucleotide agents that inhibit RNase H activity of a retroid virus reverse transcriptase and are useful for inhibiting retroid virus proliferation and preventing or treating a retroid virus infection.

Growing community of inventors

St-Hubert, Canada

Masad Jose Damha