公开(公告)号：US20240366793A1

公开(公告)日：2024-11-07

申请号：US18653868

申请日：2024-05-02

Applicant: California Institute of Technology

Inventor： Ishaan J. Dev ,  Mengtong Duan ,  Mikhail G. Shapiro

IPC: A61K48/00 ,  C12N15/11 ,  C12N15/85

Abstract: Disclosed herein include methods, compositions, and kits enabling expression of multiple payload proteins from a single mRNA configured to achieve a predetermined stoichiometry of first unit payload protein(s) and second unit payload protein(s) in a cell or cell-like environment. There are provided, in some embodiments, nucleic acid compositions comprising a polynucleotide comprising a first nucleic acid unit (encoding one or more first unit payload protein(s)) and a second nucleic acid unit (encoding one or more second unit payload protein(s)). The first nucleic acid unit and the second nucleic acid unit can each comprise an engineered translation initiation site (eTIS) comprising a three-nucleotide tunable element immediately upstream of a start codon. In some embodiments, the nucleic acid composition comprises at least one modified nucleotide and/or at least one nucleotide analogue or nucleotide derivative. In some embodiments, the polynucleotide comprises a disclosed eTIS combination.