49 results about "Antisense RNA" patented technology

The invention provides annular multi-tandem PCSK9 siRNA, which comprises at least one positive-sense strand sequence and at least one spacer sequence. The sense strand of the cyclic siRNA is derived from an engineered parent DNA template containing all essential sequences, comprising in the following order a first cyclization element, optionally at least one first restriction enzyme recognition sequence, at least one target sequence, optionally at least one second restriction enzyme recognition sequence, and a second cyclization element. The annular multi-tandem RNA positive-sense strand can combine and deliver a plurality of antisense strand RNAs, and the combination of the positive-sense strand and the antisense strand is increased while the stability advantage of the annular RNA is utilized.

The present invention comprises a pharmaceutic composition comprising one or more hepatocyte nuclear factor four alpha antisense RNA 1 (HNF4A-AS1) targeting polynucleotides, wherein the one or more HNF4A-AS1 targeting polynucleotides is capable of repressing HNF4A-AS1 in a subject resulting in upregulation of HNF4A expression and / or increasing HNF4A P1:P2 isoform ratio in the subject. The present invention also provides a method of treatment of a HNF4A-associated disease in a subject comprising the step of administering a therapeutically effective amount of the pharmaceutical composition comprising one or more HNF4A- AS1 targeting polynucleotides of the present invention. The present invention also provides a method of downregulating HNF4A P2 isoform expression in a subject comprising the step of repressing HNF4A-AS1 in the subject.

The present invention comprises a pharmaceutic composition comprising one or more hepatocyte nuclear factor four alpha antisense RNA 1 (HNF4A-AS1) targeting polynucleotides, wherein the one or more HNF4A-AS1 targeting polynucleotides is capable of repressing HNF4A-AS1 in a subject resulting in upregulation of HNF4A expression and / or increasing HNF4A P1:P2 isoform ratio in the subject. The present invention also provides a method of treatment of a HNF4A-associated disease in a subject comprising the step of administering a therapeutically effective amount of the pharmaceutical composition comprising one or more HNF4A- AS1 targeting polynucleotides of the present invention. The present invention also provides a method of downregulating HNF4A P2 isoform expression in a subject comprising the step of repressing HNF4A-AS1 in the subject.

The present invention relates to lipid compounds, which can be used alone or in combination with other lipid components such as neutral lipids, charged lipids, steroids and / or their analogs, and / or lipid-conjugated polymers to form lipid nanoparticles for delivering therapeutic and / or prophylactic agents. In some instances, the lipid nanoparticles are used to deliver nucleic acids, such as messenger RNA and / or antisense RNA. Methods of using such lipid nanoparticles to treat and / or prevent various diseases are also provided. In one embodiment, a compound having the structure of formula (I) is provided: or a salt or an isomer or an N-oxide thereof, wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein. Pharmaceutical compositions comprising one or more of the compounds of the foregoing structural formula (I) and a therapeutic and / or prophylactic agent are also provided. In some embodiments, the pharmaceutical composition further comprises one or more components selected from neutral lipids, charged lipids, steroids and lipid-conjugated polymers. Such compositions are useful for forming lipid nanoparticles for delivering therapeutic and / or prophylactic agents. In other embodiments, the present invention provides a method of administering a therapeutic and / or prophylactic agent to a subject in need thereof, the method comprising preparing a pharmaceutical combination of a lipid nanoparticle comprising a compound of structural formula (I) and a therapeutic and / or prophylactic agent, and delivering the composition to the subject.

This disclosure relates to a nucleic acid comprising a double stranded RNA molecule comprising sense and antisense strands and further comprising a single stranded DNA molecule covalently linked to at least the 5′ end of either the sense or antisense RNA part of the molecule wherein the double stranded inhibitory RNA targets genes associated with cardiovascular disease in the treatment hypercholesterolemia and diseases associated with hypercholesterolemia such as cardiovascular disease.

The invention relates to the field of gene engineering, in particular to a cascade reaction-based plasmid elimination module, which comprises three types of mutually independent expression regions, one type of the expression regions is an antisense RNA expression region and comprises antisense RNA, a promoter of the antisense RNA and a terminator, and the other type of the expression regions is an antisense RNA expression region and comprises antisense RNA, a promoter of the antisense RNA and a terminator of the antisense RNA. The antisense RNA is the antisense RNA of a metabolic key gene mRNA, and can be combined with the metabolic key gene mRNA to hinder the translation of the metabolic key gene mRNA; the first region is an antisense neutralizing RNA expression region and comprises antisense neutralizing RNA, an inducible promoter of the antisense neutralizing RNA and a terminator of the antisense neutralizing RNA; the last type of region is a transcription factor region and is composed of constitutive promoters carried by a transcription factor fragment, and the constitutive promoters comprise an RNA polymerase binding site, a transcription start site, a ribosome binding site, a transcription factor translation region and a terminator; the antisense neutralizing RNA is an RNA fragment which is complementary with the antisense RNA in sequence, can be combined with the antisense RNA to enable the antisense RNA not to be combined with the metabolic key gene mRNA, and inhibits the antisense RNA from generating translation obstruction on the metabolic key gene mRNA. The method is high in elimination efficiency, elimination objects can be freely set according to needs, and selective or synchronous elimination of various plasmids can be realized.

To provide compositions and methods for the treatment of leukodystrophy.SOLUTION: Provided is use of administering an effective amount of a compound that down-modulates the expression of both wild-type and mutant TUBB4-A in the manufacture of a pharmaceutical composition for the treatment or prevention of hypomyelination and atrophy of the basal ganglia (H-ABC) leukodystrophy, the pharmaceutical composition ameliorating symptoms of H-ABC, and the compound being selected from short hairpin RNA (shRNA), short interfering RNA (siRNA), antisense RNA, antisense DNA, chimeric antisense DNA / RNA, microRNA, and a ribozyme that is sufficiently complementary to either the gene or mRNA encoding TUBB4A.SELECTED DRAWING: Figure 1-1

The present invention relates to lipid compounds, which can be used alone or in combination with other lipid components such as neutral lipids, charged lipids, steroids and / or their analogues, and / or lipid-conjugated polymers to form lipid nanoparticles for delivering therapeutic and / or prophylactic agents. In some examples, the lipid nanoparticles are used to deliver nucleic acids, such as messenger RNA and / or antisense RNA. Methods of using such lipid nanoparticles to treat and / or prevent various diseases are also provided. In one embodiment, a compound having the structure of formula (I) is provided: or a salt or an isomer or an N-oxide thereof, wherein R 1 , R 2 as defined herein. There is also provided a pharmaceutical composition comprising one or more compounds of the foregoing structural formula (I) and a therapeutic and / or prophylactic agent. In some embodiments, the pharmaceutical composition further comprises one or more components selected from neutral lipids, charged lipids, steroids and lipid-conjugated polymers. Such compositions are useful for forming lipid nanoparticles for delivering therapeutic and / or prophylactic agents. In other embodiments, the present invention provides a method of administering a therapeutic and / or prophylactic agent to a subject in need thereof, the method comprising preparing a pharmaceutical combination of a lipid nanoparticle comprising a compound of structural formula (I) and a therapeutic and / or prophylactic agent, and delivering the composition to the subject.

The invention relates to lipid compounds which can be used alone or in combination with other lipid components such as neutral lipids, charged lipids, steroids and / or their analogues, and / or lipids conjugated with polymers to form lipid nanoparticles for delivering therapeutic and / or prophylactic agents. In some examples, the lipid nanoparticles are used for delivering nucleic acids such as messenger RNA and / or antisense RNA. Methods of using such lipid nanoparticles to treat and / or prevent various diseases are also provided. In one embodiment, a compound having the structure of formula (I) is provided: or a salt or an isomer or an N-oxide thereof, wherein R1, R2 and R3 are as defined herein. A pharmaceutical composition comprising one or more of the compounds of the foregoing structural formula (I) and a therapeutic and / or prophylactic agent is also provided. In some embodiments, the pharmaceutical composition further comprises one or more components selected from neutral lipids, charged lipids, steroids and lipids conjugated with polymers. Such compositions are useful for forming lipid nanoparticles for delivering therapeutic and / or prophylactic agents. In other embodiments, the invention provides a method of administering a therapeutic and / or prophylactic agent to a subject in need thereof, the method comprising preparing a pharmaceutical combination of a lipid nanoparticle comprising a compound of structural formula (I) and a therapeutic and / or prophylactic agent, and delivering the composition to the subject.

The present invention relates to lipid compounds which can be used alone or in combination with other lipid components such as neutral lipids, charged lipids, steroids and / or their analogues, and / or lipid-conjugated polymers to form lipid nanoparticles for delivering therapeutic and / or prophylactic agents. In some examples, the lipid nanoparticles are used for delivering nucleic acids such as messenger RNA and / or antisense RNA. Also provided are methods of using such lipid nanoparticles for treating and / or preventing various diseases. In one embodiment, a compound having the structure of formula (I) is provided: or a salt or an isomer or an N-oxide thereof, wherein R1 is as defined herein. Also provided is a pharmaceutical composition comprising one or more compounds of the foregoing structural formula (I) and a therapeutic and / or prophylactic agent. In some embodiments, the pharmaceutical composition further comprises one or more components selected from neutral lipids, charged lipids, steroids and lipid-conjugated polymers. Such compositions are useful for forming lipid nanoparticles for delivering therapeutic and / or prophylactic agents. In other embodiments, the present invention provides a method of administering a therapeutic and / or prophylactic agent to a subject in need thereof, the method comprising preparing a pharmaceutical combination of a lipid nanoparticle comprising a compound of structural formula (I) and a therapeutic and / or prophylactic agent, and delivering the composition to the subject.

The invention relates to the field of biological medicine, in particular to application of an IL7R inhibitor in preparation of a medicine for treating rosacea. The IL7R inhibitor comprises preparations for inhibiting the IL7R at the gene level and the protein level, the preparations for inhibiting the IL7R at the gene level comprise shRNA, siRNA, dsRNA, miRNA, cDNA and antisense RNA / DNA, and the preparations for inhibiting the IL7R at the protein level comprise small molecule compounds, peptides and antibodies. It is found for the first time that the targeted IL7R has a remarkable treatment effect on rosacea, the recurrence rate can be effectively reduced, and the skin lesion degree can be relieved. The discovery not only opens up a new direction for fundamental research of rosacea, but also provides a brand-new and breakthrough solution for clinical treatment of rosacea, and is expected to bring a more durable and stable treatment effect for patients.

This invention generally relates to a novel composition of RNA / mRNA medicines as well as vaccines produced by using replicase- and / or RNA-dependent RNA polymerase (RdRp)-mediated RNA cycling reaction (RCR). The present invention is useful for developing a variety of self-amplifying RNA / mRNA (samRNA) medicines and vaccines containing at least a replicase / RdRp-binding site in the 5′- or 3′-end, or both, of any desired RNA molecule, including but not limited to antisense RNA (aRNA), small interfering RNA (siRNA), short hairpin RNA (shRNA), microRNA (miRNA) / miRNA precursor, long non-coding RNA (lnRNA) and mRNA. These RNA molecules can be either in single-stranded or in double-stranded, or mixed, conformation. The samRNA so obtained is useful not only for producing RNA-based vaccines and / or medicines but also for generating the mRNA-associated proteins, peptides, and / or antibodies under a proper in-vitro or in-cell translation condition. The replicase / RdRp-binding sites used in samRNA are derived or modified from coronaviral (e.g. COVID-19) and / or hepatitis C viral (HCV) RNA-dependent RNA polymerases (RdRp) in either single-stranded or double-stranded compositions.

The present invention relates to lipid compounds, which can be used alone or in combination with other lipid components such as neutral lipids, charged lipids, steroids and / or their analogs, and / or lipid-conjugated polymers to form lipid nanoparticles for delivering therapeutic and / or prophylactic agents. In some instances, the lipid nanoparticles are used to deliver nucleic acids, such as messenger RNA and / or antisense RNA. Also provided are methods of using such lipid nanoparticles to treat and / or prevent various diseases. In one embodiment, a compound having the structure of formula (I) is provided: or a salt or an isomer or an N-oxide thereof, wherein X is as defined herein. Also provided is a pharmaceutical composition comprising one or more of the compounds of the foregoing structural formula (I) and a therapeutic and / or prophylactic agent. In some embodiments, the pharmaceutical composition further comprises one or more components selected from neutral lipids, charged lipids, steroids, and lipid-conjugated polymers. Such compositions are useful for forming lipid nanoparticles for delivering therapeutic and / or prophylactic agents. In other embodiments, the present invention provides a method of administering a therapeutic and / or prophylactic agent to a subject in need thereof, the method comprising preparing a pharmaceutical combination of a lipid nanoparticle comprising a compound of structural formula (I) and a therapeutic and / or prophylactic agent, and delivering the composition to the subject.

The invention belongs to the technical field of biological medicines, and particularly relates to a multi-target programmable dsRNA delivery platform and application thereof in pest control. The dsRNA delivery platform is a self-assembled micron-sized microsphere containing a target sequence, and the target sequence can be replaced by other pest and disease damage sequences; the target sequence comprises a positive-sense RNA (Ribonucleic Acid) with a complementary sequence as shown in SEQ ID No. 1 and an antisense RNA with a sequence as shown in SEQ ID No. 2. The positive-sense RNA has a complementary sequence as shown in SEQ ID No. 1. The delivery platform delivers the dsRNA in a targeted manner, the degradation rate of the dsRNA in a plant leaf surface environment can be remarkably reduced, mRNA of a corresponding targeted gene is specifically cut, and metabolic disorder of pests is caused, so that normal physiological activities of the pests are blocked, and the purpose of preventing and treating the pests is achieved.

The invention discloses a production technology flow of largemouth bass with delayed gonad development, and belongs to the technical field of aquatic animal biological breeding. The method comprises the following steps: breeding parents, designing an antisense RNA sequence, amplifying, preparing a transfection reagent, carrying out artificial insemination on the micropterus salmoides, and introducing the antisense RNA sequence of a sex development key gene, thereby creating a new germplasm of the micropterus salmoides with remarkably improved growth speed, remarkably reduced gonad index and better muscle quality and flavor; the technical support is provided for promoting the high-quality sustainable development of the largemouth bass industry.

The invention discloses antisense RNA for targeted inhibition of infectious spleen and kidney necrosis virus, a recombinant vector, a kit and application of the antisense RNA. The antisense RNA is selected from at least one of antisense RNA1 and antisense RNA2; wherein the nucleotide sequences for coding the antisense RNA1 and the antisense RNA2 are respectively as shown in SEQ ID NO.1-2. The invention also discloses a preparation method of the antisense RNA1 and the antisense RNA2. In order to solve the problem that the ISKNV lacks an effective prevention and control means, the long-chain antisense RNA is designed by selecting a virus ORF69 (non-functional protein) and a membrane protein Allo46 as double targets for the first time, the antisense RNA designed by the invention can directly block virus proliferation, the long sequence design tolerates target mutation, and meanwhile, double-target synergistic inhibition can improve the efficiency and delay virus escape. The recombinant vector is introduced into the mandarin fish fries to prepare the anti-ISKNV mandarin fish fries, so that virus outbreak triggered by water temperature can be prevented and controlled from the source, and the economic loss of culture is effectively reduced.

Provided is a recombinant oncolytic virus composition, comprising a first recombinant oncolytic virus and a second recombinant oncolytic virus. Both the first and second recombinant oncolytic viruses comprise a herpes simplex virus vector and an exogenous gene, the exogenous gene is encoded from one of cytokine, a monoclonal antibody having a tumor preventative and / or treatment function, tumor antigens, prodrug invertase, tumor suppressor polypeptide, antisense RNA or small RNA, wherein the exogenous genes in the first and the second recombinant oncolytic viruses are different. Also provided is an application of the recombinant oncolytic virus composition in preparation of a medicament drug for treating tumors.

This invention generally relates to a novel induced cytoplasmic IVT (ICIVT) composition useful for inducing in-vitro transcription (IVT)-like RNA / mRNA amplification in the cells of interest after transfection in vitro, ex vivo and / or in vivo. The present invention is useful for designing and developing a variety of RNA / mRNA medicines as well as vaccines comprising a mixture of at least a promoter-linked RNA / mRNA-coding DNA (PLRcD) template and another DNA-dependent RNA polymerase (DdRP) mRNA sequence. Preferably, the DdRP mRNA may be selected from the mRNA of T7, T3 and / or SP6 RNA polymerase, or a combination thereof, while the PLRcD template may encode the transcripts of antisense RNA oligonucleotide (aRNA-ASO), small interferring RNA (siRNA), double-stranded RNA (dsRNA), short hairpin RNA (shRNA), microRNA (miRNA) / microRNA precursor (pre-miRNA), long noncoding RNA (IncRNA), messenger RNA (mRNA), and / or self-amplifying RNA / mRNA (saRNA / samRNA), or a combination thereof.

Described herein are compositions, pharmaceutical compositions, kits, and methods of use relating to anti-Dio3os antisense RNA. In embodiments, antisense Dio3os compositions, kits, and methods are described to improve symptoms of osteoporosis, for example, osteoporosis induced by a disorder characterized by a thyroid hormone imbalance (i.e., hyperthyroidism or hypothyroidism). In embodiments, antisense Dio3os compositions, kits, and methods are described to improve sensitivity of cancer cells to anti-cancer therapeutics, for example, sensitivity of ER+ breast cancer or other breast cancer cells, thyroid cancer cells, prostate cancer cells, hepatocellular cancer cells, pancreatic cancer cells, and ovarian cancer cells that are sensitized or otherwise non-responsive to cancer therapeutics (for example, aromatase inhibitors or HDAC inhibitors). Combination therapies are also contemplated utilizing antisense RNA according to the present disclosure and other drugs, for example, thyroid and anti-cancer medications.

The invention relates to the technical field of agricultural biology, in particular to dsRNA of a pinus massoniana gene11 gene and application of the dsRNA, and the dsRNA is composed of a sense RNA chain shown in SEQ ID NO: 1 and an antisense RNA chain reversely complementary with the sense RNA chain. According to the dsRNA of the pine caterpillars gene11 gene and the preparation method and application thereof, the dsRNA is injected into pine caterpillars, target genes of the pine caterpillars are efficiently silenced, the death rate of the pine caterpillars can be increased, feeding behavior taxis is reduced, food digestion is affected, and finally the prevention and treatment effect is achieved; and a new effective way is provided for preventing and treating the pine caterpillars.

The present application relates to the field of biological medicine, and particularly relates to application of IL7R inhibitor in preparation of a drug for treating rosacea. The IL7R inhibitor includes preparations for inhibiting the IL7R at the gene level and the protein level, the preparation for inhibiting the IL7R at the gene level is shRNA, siRNA, dsRNA, miRNA, cDNA, antisense RNA / DNA, and the preparation for inhibiting the IL7R at the protein level is a small molecule compound, a peptide and an antibody. It is found for the first time that targeting IL7R has a significant therapeutic effect on rosacea, can effectively reduce the recurrence rate and reduce the degree of skin lesions. This finding not only opens up a new direction for the basic research of rosacea, but also provides a brand-new and breakthrough solution for the clinical treatment of rosacea, and is expected to bring more persistent and stable therapeutic effect for patients.

The present invention relates to lipid compounds which can be used alone or in combination with other lipid components such as neutral lipids, charged lipids, steroids and / or their analogues, and / or lipid-conjugated polymers to form lipid nanoparticles for delivering therapeutic and / or prophylactic agents. In some instances, the lipid nanoparticles are used to deliver nucleic acids such as messenger RNA and / or antisense RNA. Methods of using such lipid nanoparticles to treat and / or prevent various diseases are also provided. In one embodiment, a compound having the structure of formula (I) is provided: or a salt or an isomer or an N-oxide thereof, wherein R 1 , R 2 and R 3 are as defined herein. Pharmaceutical compositions comprising one or more of the compounds of formula (I) above and a therapeutic and / or prophylactic agent are also provided. In some embodiments, the pharmaceutical composition further comprises one or more components selected from neutral lipids, charged lipids, steroids and lipid-conjugated polymers. Such compositions are useful for forming lipid nanoparticles for delivering therapeutic and / or prophylactic agents. In other embodiments, the present invention provides a method of using a therapeutic and / or prophylactic agent in a subject in need thereof, the method comprising preparing a pharmaceutical combination of a lipid nanoparticle comprising a compound of formula (I) and a therapeutic and / or prophylactic agent and delivering the composition to the subject.

The application discloses a production technical process of gonad delayed development of large-mouth bass, and belongs to the technical field of aquatic animal biological breeding. The application creates new germplasm of large-mouth bass with significantly improved growth speed, significantly decreased gonad index and better muscle quality and flavor by parent cultivation, design of antisense RNA sequence and amplification, artificial insemination of the large-mouth bass after preparation of transfection reagent and introduction of the antisense RNA sequence of a key gender development gene, thereby providing technical support for promoting high-quality and sustainable development of the large-mouth bass industry.

The invention relates to the field of gene engineering, in particular to a plasmid elimination module based on an inducible promoter, which comprises two types of mutually independent expression regions, one type of region is an inducible factor transcription region, and the inducible factor transcription region is composed of a constitutive promoter carried by an inducible transcription factor fragment, and the other type of region is an inducible transcription factor fragment. The kit comprises an RNA polymerase binding site, a transcription start site, a ribosome binding site, an induced transcription factor translation region and a terminator, the other region is an antisense RNA expression region and comprises an inducible factor promoter corresponding to an inducible transcription factor, an antisense RNA and a terminator; the antisense RNA is the antisense RNA of the metabolic key gene mRNA, and can be combined with the metabolic key gene mRNA to hinder the translation of the metabolic key gene mRNA. The method is high in elimination efficiency, elimination objects can be freely set according to needs, and selective or synchronous elimination of various plasmids can be realized.

Interfering nucleic acids and methods of their use in treat prostate cancers, such as aggressive prostate cancers. The nucleic acids may be, for example, short interfering RNA (siRNA), short hairpin RNA (shRNA), antisense RNA, DNA, antisense DNA, Chimeric Antisense DNA / RNA, and microRNA (miRNA) oligonucleotides. The oligonucleotide has a seed sequence that is complementary to a sequence of either a gene or an mRNA encoding an androgen receptor (AR) coregulator or a fragment having AR coregulator activity. The nucleic acid compound may have a non-natural modification in the oligonucleotide, and / or an organic moiety conjugated to the oligonucleotide. The oligonucleotide has inhibitory activity against the expression or biological activity of the AR coregulator.

The present invention provides a composition comprising one or more polynucleotides capable of upregulating expression of telomerase wherein telomerase consists of a protein component with reverse transcriptase activity encoded by telomerase reverse transcriptase (TERT) gene and a non-coding RNA encoded by telomerase RNA component (TERC) gene, In an embodiment, the one or more polynucleotides of the present invention upregulates the telomerase by downregulating antisense RNA that regulates telomerase gene. In an embodiment, the one or more polynucleotides comprises an siRNA or an shRNA. In an embodiment, one or more polynucleotides of the present invention is delivered by a nanoparticle such as an exosome that encapsulates the one or more polynucleotides. The present invention also provides a method of treatment of telomerase deficiency related diseases or disorders using any embodiment of the one or more polynucleotides of the present invention.

A novel gene modulation technique for modulating target nucleic acid and / or protein levels in cells, tissues, organisms and animals is disclosed. The new technology provides compositions for gene modulation applications, including prevention and treatment of human diseases. The composition comprises a short antisense RNA (asRNA) molecule having at least one deoxynucleotide monomer spacer motif. The invention further provides methods of using the compositions to modulate the expression or function of a target gene, to treat or prevent disease, and for biomedical research, disease diagnosis, and other biological applications.

The present invention relates to lipid compounds which can be used alone or in combination with other lipid components such as neutral lipids, charged lipids, steroids and / or their analogs, and / or lipid-conjugated polymers to form lipid nanoparticles for delivering therapeutic and / or prophylactic agents. In some instances, the lipid nanoparticles are used to deliver nucleic acids such as messenger RNA and / or antisense RNA. Also provided are methods of using such lipid nanoparticles to treat and / or prevent various diseases, wherein the structural formula I of the compound is as follows: or a salt or an isomer or an N-oxide thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are as defined herein.

The present invention provides a composition comprising one or more polynucleotides capable of upregulating expression of alpha- 1 anti-trypsin (Al AT). In an embodiment, the one or more polynucleotides of the present invention upregulates the expression of Al AT by downregulating antisense RNA that regulates the Al AT gene. In an embodiment, the one or more polynucleotides comprises an siRNA or an shRNA. In an embodiment, one or more polynucleotides of the present invention is delivered by a nanoparticle such as an exosome that encapsulates the one or more polynucleotides. The present invention also provides a method of treatment of Al AT deficiency related diseases or disorders using any embodiment of the one or more polynucleotides of the present invention.

An HTT nucleic acid trans-splice molecule is described that includes a coding domain comprising one or more HTT exons, a splice site, and a binding domain that binds to a target intron of an HTT precursor mRNA. The HTT nucleic acid trans-splice molecules described herein may also be used in combination with, for example, an MSH3 binding domain aligned in series with an HTT binding domain, an MSH3 nucleic acid trans-splice molecule, an MSH3 splice modulator, an antisense oligonucleotide or antisense RNA for either of MSH3 or HTT, and an MSH3 or HTT microRNA (miRNA) and constructs encoding them. Also encompassed are compositions comprising the nucleic acid trans-splice molecules described herein, as well as compositions comprising a nucleic acid trans-splice molecule in combination with an additional therapeutic agent (e.g., an MSH3 nucleic acid trans-splice molecule, an MSH3 splice modulator, an antisense oligonucleotide or antisense RNA for any one of MSH3 or HTT). The nucleic acid trans-splicing molecules may be used alone or in combination with additional therapeutic agents in methods of treating Huntington's disease (HD). Also described herein are nucleic acid trans-splice molecules for use in the treatment of HD or in the preparation of medicaments for the treatment of HD, alone or in combination with additional therapeutic agents. Also encompassed herein are MSH3 nucleic acid trans-splice molecules, MSH3 splice modulators, and MSH3 miRNAs, as well as constructs encoding them, which can be used, alone or in combination and / or in combination with additional therapeutic agents, for the treatment of nucleotide repeat disorders (e.g., HD) or for the preparation of medicaments for the treatment of nucleotide repeat disorders (e.g., HD).