Nuclease Resistant Polynucleotides and Uses Thereof
AssigneeTranslate Bio, Inc.
InventorsMichael Heartlein, Braydon Charles Guild, Frank DeRosa
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Abstract
The invention provides, among other things, methods of stabilizing mRNA and nuclease resistant mRNA prepared in accordance with such methods. In certain embodiments, the nuclease resistant mRNA encodes a functional protein, such as enzyme, and is characterized by its resistance to nuclease digestion, increased half-life and/or its ability to produce increased amounts of the functional protein (e.g., enzyme) encoded thereby.
Claims19
A method of modulating the nuclease resistance of a polynucleotide having a coding region and a non-coding region, the method comprising a step of contacting the polynucleotide with a stabilizing oligonucleotide, thereby modulating the nuclease resistance of the polynucleotide, wherein the stabilizing oligonucleotide is complementary to the non-coding region of the polynucleotide and comprises at least one modified nucleobase.
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9-32. (canceled)
35-39. (canceled)
A nuclease resistant mRNA comprising mRNA having a coding region and a non-coding region and a complementary stabilizing oligonucleotide hybridized to at least a portion of the non-coding region of the mRNA, wherein the stabilizing oligonucleotide comprises at least one modified nucleobase, and wherein the nuclease resistant mRNA is more resistant to nuclease degradation relative to the un-hybridized mRNA.
41-64. (canceled)
A method of increasing translation of polypeptide from an mRNA transcript having a coding region and a non-coding region, the method comprising a step of hybridizing a stabilizing oligonucleotide to a portion of the non-coding region of the mRNA transcript thereby increasing amount of the polypeptide translated from the mRNA transcript;
- and wherein the stabilizing oligonucleotide comprises at least one modified nucleobase.
67-86. (canceled)
A method of increasing translation of an exogenous mRNA transcript having a coding region and a non-coding region, the method comprising a step of co-administering the exogenous mRNA transcript with a stabilizing oligonucleotide into a cell;
- wherein the stabilizing oligonucleotide is complementary to the non-coding region of the mRNA transcript;
- wherein the co-administering results in increased translation of the exogenous mRNA transcript;
- and wherein the stabilizing oligonucleotide comprises at least one modified nucleobase.
88-119. (canceled)
Dependencies are inferred from the claim text.