US20260263638
2026-09-10
Human necessities
A61K48/005
The patent application discusses novel compositions and methods for enhancing RNA properties through modifications at the 5′ cap region of RNA molecules. These modifications involve the inclusion of altered nucleotides at position +3 or higher, relative to the 5′ terminus. The aim is to improve the stability and translation efficiency of RNA, which is crucial for therapeutic applications. The document also outlines methods for synthesizing these modified RNA transcripts and their potential use in various medical treatments.
Messenger RNA (mRNA) technology is gaining traction as a promising alternative to traditional therapeutics and vaccines due to its potency and programmability. Despite its potential, mRNA therapy faces challenges such as instability, toxicity, and short-term efficacy. These issues hinder its broader application in clinical settings. Enhancing the stability and translation efficiency of mRNA is essential to overcoming these challenges and improving its therapeutic potential.
The application focuses on extending chemical modifications beyond the first two bases of the mRNA, which is a novel approach. These modifications are introduced at or beyond position +3 in the 5′ untranslated region (5′ UTR), aiming to increase the stability and efficiency of mRNA in cells and in vitro systems. The modifications are achieved through specific chemical processes, including the use of nonpolar counterions and solid-phase synthesis.
The disclosed method involves several steps: synthesizing a 5′-phosphorylated RNA oligonucleotide, capping it chemically, purifying the capped RNA, and ligating it to an RNA precursor. The process ensures that a high percentage of the RNA oligonucleotides are capped, enhancing their stability. Various embodiments of the method include chemical capping with imidazole, circularizing RNA transcripts, and introducing azide handles for click chemistry. The purification is typically performed using high-performance liquid chromatography (HPLC).
The modified RNA compositions have potential therapeutic applications, including the production of therapeutic proteins and vaccines. The patent outlines various embodiments concerning the length and composition of the RNA oligonucleotides, as well as the types of modifications, such as modified sugars and phosphates. These modifications can significantly impact the RNA's properties, making it more suitable for clinical applications.