Internal ribosome entry sites for improved polynucleotide translation

• Main Authors: ANDRIANOVA, ELIZAVETA, METKAR, MIHIR, JAIN, RUCHI
• Format: Patent
• Language: Chinese; English
• Published: 01.05.2024
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPIRITS; VINEGAR; WINE

This disclosure relates to internal ribosome entry site (IRES) elements that are capable of effectuating expression of a desired polynucleotide even in the absence of a 5' cap structure. The disclosure also provides polynucleotides (e.g., RNA molecules, such as circular or linear RNA molecules) containing such IRES elements. In some embodiments of the disclosure, the IRES element contains one or more nucleic acid segments that are enriched in uridine nucleosides or modified uridine nucleosides, such as 1-methylpseudouridine nucleosides. In some embodiments, the IRES element contains one or more nucleic acid segments that feature a plurality of contiguous uridine nucleosides or modified uridine nucleosides (e.g., 1-methylpseudouridine nucleosides). In some embodiments, the IRES elements described herein can recruit ribosomes and/or translation initiation factors by, e.g., binding to ribosomes, hybridizing to the ribosomal RNA of a ribosome, or binding to translation initiation factors. The polynucleotides (e.g