Hybrid oligonucleotides
AssigneeEntrada Therapeutics, Inc.
InventorsIreneusz NOWAK, Ziqing QIAN, Mahboubeh KHEIRABADI
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Abstract
Provided herein are methods for making hybrid oligonucleotides, hybrid oligonucleotides, and compounds and compositions comprising hybrid oligonucleotides.
Claims20
1-94. (canceled)
A hybrid oligonucleotide comprising:
- (i) a first nucleotide sequence consisting of a series of two or more morpholino nucleotide analogs linked by phophorodiamidate linkages and comprising a 6′ end and a 3′ end;
- (ii) a second nucleotide sequence consisting of a series of two or more deoxyribonucleotides or analogs thereof and/or ribonucleotides or analogs thereof and comprising a 5′ end and a 3′ end;
- and
- (iii) a phosphorothioamidate linkage that links the terminal 3′ nucleic acid residue of the first nucleotide sequence and the terminal 5′ nucleic acid residue of the second nucleotide sequence.
A method of making a hybrid oligonucleotide comprising assembling P(III) and P(V) nucleotides in a 6′ to 3′ or 5′ to 3′ direction on a support and employing PMO 6′-phosphoramidite P(III) or phosphoramidate P(V) as the first nucleotide from the support, wherein at least one of the assembled P(III) and P(V) nucleotides is a first morpholino nucleotide analog and at least one of the P(III) and P(V) assembled nucleotides is a first reverse RNA or a first reverse DNA nucleotide or nucleotide analog, and the method comprises connecting the first morpholino nucleotide analog to the first reverse RNA or the first reverse DNA nucleotide or nucleotide analog via a phosphorothioamidate linkage.
A method of making a hybrid oligonucleotide comprising assembling P(III) and P(V) nucleotides in a 6′ to 3′ or 5′ to 3′ direction on a support and employing PMO 6′-phosphoramidite P(III) as the first nucleotide from the support.
A hybrid oligonucleotide comprising a plurality of morpholino nucleotide analogs and a plurality of RNA or DNA nucleotides or nucleotide analogs, wherein each morpholino nucleotide analog that is linked to an adjacent RNA or DNA nucleotide or nucleotide analog is linked to the adjacent RNA or DNA nucleotide or nucleotide analog via a phosphorothioamidate linkage.
Dependencies are inferred from the claim text.