Synthetic Transfer Rna with Modified Nucleotides

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This invention relates to synthetic transfer RNAs (tRNAs) that are engineered to contain specific, non-naturally occurring modifications at particular nucleotide positions. These modifications are chosen to reduce the immune response (immunogenicity) to the tRNA when used in a therapeutic context, while retaining or enhancing the tRNA's ability to function in the protein synthesis machinery of cells. The invention is particularly aimed at enabling tRNA-based drugs to efficiently suppress genetic mutations (e.g., premature stop codons and frameshift mutations) that cause disease, with minimized immune side effects.

Use CasesContent extracted from patent full text and abstract with AI.

• Gene therapy for genetic diseases caused by nonsense (premature stop) or frameshift mutations, such as cystic fibrosis, Duchenne muscular dystrophy, beta-thalassemia, Hurler syndrome, Tay-Sachs disease, neurofibromatosis type 1, Crohn's disease, and neuronal ceroid lipofuscinosis.
• Suppression or correction of premature termination codons (PTC) in mRNA to restore production of full-length, functional proteins.
• Supplementation of tRNAs in conditions where a specific tRNA is sequestered or deficient, such as Charcot-Marie-Tooth disease.
• Development of personalized or disease-focused RNA-based therapeutics with lowered immunogenicity.
• Biotechnological or research applications requiring stable, functional synthetic tRNAs with custom anticodons and minimal activation of immune responses.
• Potential use in mRNA-based interventions when paired with synthetic tRNAs for improved protein translation.

BenefitsContent extracted from patent full text and abstract with AI.

• Enables the design and use of synthetic tRNAs for therapeutic purposes with much lower risk of triggering immune responses, compared to unmodified or conventionally modified tRNAs.
• Allows treatment of a wide range of genetic diseases caused by nonsense or frameshift mutations by restoring the translation of full-length proteins.
• Improves the stability and cellular uptake of therapeutic tRNAs owing to specific modifications, potentially leading to higher efficacy at lower doses.
• Reduces or eliminates side effects related to immune system activation, making repeated or systemic administration more feasible.
• Customized modifications at specific positions allow fine-tuning of both function and immunogenicity according to therapeutic needs.
• Combination of selected nucleotide modifications achieves synergy in maintaining tRNA activity and suppressing immune responses, as demonstrated by examples (e.g., Gm18 & PseudoU60).
• Applicable to a broad range of delivery methods, including viral vectors and lipid nanoparticles.

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Inventors & Applicants

Patent Abstract

The invention relates to a synthetic transfer RNA with at least one modified nucleotide or combination of modified nucleotides at a unique position or a unique pattern of modified nucleotides.