Recognizing the translocation signals of individual peptide–oligonucleotide conjugates using an α-hemolysin nanopore

New lipid conjugates of DNA and RNA incorporating one to four [(4-dodecylphenyl)sulfonyl]phosphoramidate or (hexadecylsulfonyl)phosphoramidate groups at internucleotidic positions near the 3′ or 5′-end were synthesized and characterized. Low cytotoxicity of the conjugates and their ability to be taken up into cells without transfection agents were demonstrated. Lipid-conjugated siRNAs targeting repulsive guidance molecules a (RGMa) have shown a comparable gene silencing activity in PK-59 cells to unmodified control siRNA when delivered into the cells via Lipofectamine mediated transfection.

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Synthesis of Carbohydrate-Oligonucleotide Conjugates and Their Applications

Enzymatic and Chemical Synthesis of Nucleic Acid Derivatives ◽

10.1002/9783527812103.ch10 ◽

2018 ◽

pp. 259-289 ◽

Cited By ~ 1

Author(s):

Juan C. Morales

Keyword(s):

Oligonucleotide Conjugates

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ChemInform Abstract: Mixture-Based Combinatorial Libraries from Small Individual Peptide Libraries: A Case Study on α-Antitrypsin Deficiency

ChemInform ◽

10.1002/chin.201440264 ◽

2014 ◽

Vol 45 (40) ◽

pp. no-no

Author(s):

Yi-Pin Chang ◽

Yen-Ho Chu

Keyword(s):

Combinatorial Libraries ◽

Peptide Libraries ◽

Small Individual ◽

Antitrypsin Deficiency ◽

Individual Peptide

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Cationic Oligospermine-Oligonucleotide Conjugates Provide Carrier-free Splice Switching in Monolayer Cells and Spheroids

Molecular Therapy — Nucleic Acids ◽

10.1016/j.omtn.2018.09.027 ◽

2018 ◽

Vol 13 ◽

pp. 483-492 ◽

Cited By ~ 2

Author(s):

Marc Nothisen ◽

Phanélie Perche-Létuvée ◽

Jean-Paul Behr ◽

Jean-Serge Remy ◽

Mitsuharu Kotera

Keyword(s):

Carrier Free ◽

Oligonucleotide Conjugates

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Protein/oligonucleotide conjugates as a cell specific PNA carrier

Nucleic Acids Symposium Series ◽

10.1093/nass/1.1.217 ◽

2001 ◽

Vol 1 (1) ◽

pp. 217-218 ◽

Cited By ~ 2

Author(s):

K. Obara ◽

T. Ishihara ◽

T. Akaike ◽

A. Maruyama

Keyword(s):

A Cell ◽

Oligonucleotide Conjugates

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PHOTOSENSITIZED AND CATALYTIC OXIDATION OF DNA BY METALLOPHTHALOCYANINE-OLIGONUCLEOTIDE CONJUGATES

Nucleosides Nucleotides & Nucleic Acids ◽

10.1081/ncn-100002531 ◽

2001 ◽

Vol 20 (4-7) ◽

pp. 1259-1262 ◽

Cited By ~ 9

Author(s):

V. V. Koval ◽

A. A. Chernonosov ◽

T. V. Abramova ◽

T. M. Ivanova ◽

O. S. Fedorova ◽

...

Keyword(s):

Catalytic Oxidation ◽

Oxidation Of Dna ◽

Oligonucleotide Conjugates

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Improving the efficiency of precise genome editing with site-specific Cas9-oligonucleotide conjugates

Science Advances ◽

10.1126/sciadv.aaz0051 ◽

2020 ◽

Vol 6 (15) ◽

pp. eaaz0051 ◽

Cited By ~ 4

Author(s):

Xinyu Ling ◽

Bingteng Xie ◽

Xiaoqin Gao ◽

Liying Chang ◽

Wei Zheng ◽

...

Keyword(s):

Genome Editing ◽

Therapeutic Potential ◽

Chemical Reactivity ◽

Specific Chemical ◽

Site Specific ◽

Additional Tool ◽

Homology Directed Repair ◽

Chemically Modified ◽

Dna Template ◽

Oligonucleotide Conjugates

Site-specific chemical conjugation of proteins can enhance their therapeutic and diagnostic utility but has seldom been applied to CRISPR-Cas9, which is a rapidly growing field with great therapeutic potential. The low efficiency of homology-directed repair remains a major hurdle in CRISPR-Cas9–mediated precise genome editing, which is limited by low concentration of donor DNA template at the cleavage site. In this study, we have developed methodology to site-specifically conjugate oligonucleotides to recombinant Cas9 protein containing a genetically encoded noncanonical amino acid with orthogonal chemical reactivity. The Cas9-oligonucleotide conjugates recruited an unmodified donor DNA template to the target site through base pairing, markedly increasing homology-directed repair efficiency in both human cell culture and mouse zygotes. These chemically modified Cas9 mutants provide an additional tool, one that is complementary to chemically modified nucleic acids, for improving the utility of CRISPR-Cas9–based genome-editing systems.

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