RNA and nucleic acid carrier including the same
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Publication Number
US-11701378-B2
Publication Date
2023-07-18
Expiration Date
Abstract
A nucleic acid carrier according to an embodiment of the present disclosure includes CpG-ODN-RNA conjugate and a porous silica particle carrying the conjugate inside pores thereof. In this regard, the nucleic acid carrier of the present invention can stably deliver loaded nucleic acid molecules to a body and release the same to a target, thereby increasing Type 1 interferon and exhibiting RNA-inherent functions.
Core Innovation
The invention relates to a nucleic acid carrier that includes a CpG oligodeoxynucleotide-RNA (CpG-ODN-RNA) conjugate carried inside pores of a porous silica particle. The porous silica particle has an average pore diameter of 7 to 30 nm, and the RNA is indoleamine 2,3-dioxygenase (IDO) siRNA. The carrier structure is defined around the CpG-ODN-RNA conjugate loading inside the pore space of the porous silica particle.
In the described carrier, the IDO siRNA is specified as a single pair of nucleotide sequences and is selected from siRNAs comprising SEQ ID NOs: 1 and 2; or SEQ ID NOs: 3 and 4; or SEQ ID NOs: 5 and 6; or SEQ ID NOs: 7 and 8; or SEQ ID NOs: 9 and 10. In further recitations, the IDO siRNA comprises siRNA of SEQ ID NOs: 11 and 12. This focuses the carrier on particular IDO siRNA sequence selections while maintaining the same CpG-ODN-RNA conjugate and porous silica pore delivery architecture.
Additional recitations define the CpG-ODN content as being any one nucleotide among SEQ ID NOs: 13 to 15, while retaining the porous silica pore diameter range of 7 to 30 nm. The described formulation also constrains the CpG-ODN-RNA conjugate coupling and particle characteristics, including linker chemistries between CpG-ODN and RNA and quantified particle properties such as zeta potential, BET surface area, and particle diameter.
Claims Coverage
The independent claims define a nucleic acid carrier with a CpG-ODN-RNA conjugate inside porous silica pores (pore diameter 7 to 30 nm) where the RNA is IDO siRNA. Across the claims, there are four main inventive feature clusters: the carrier structure with CpG-ODN-RNA conjugate, pore diameter limitation, specific IDO siRNA sequence pair/selection (or a specific IDO siRNA comprising SEQ ID NOs 11 and 12), and specific CpG-ODN selection by SEQ ID NOs 13 to 15.
CpG-ODN-RNA conjugate loaded inside porous silica pores
A nucleic acid carrier comprising a CpG oligodeoxynucleotide-RNA (CpG-ODN-RNA) conjugate; and a porous silica particle carrying the CpG-ODN-RNA conjugate inside pores thereof, the porous silica particle having an average pore diameter of 7 to 30 nm.
IDO siRNA as the RNA component with defined sequence pair options
The RNA is indoleamine 2,3-dioxygenase (IDO) siRNA; and the IDO siRNA is a single pair of nucleotide sequences selected from siRNA comprising SEQ ID NOs: 1 and 2; 3 and 4; 5 and 6; 7 and 8; or 9 and 10.
IDO siRNA comprising siRNA of SEQ ID NOs: 11 and 12
The RNA is indoleamine 2,3-dioxygenase (IDO) siRNA; and the IDO siRNA comprises siRNA of SEQ ID NOs: 11 and 12.
CpG-ODN limited to SEQ ID NOs: 13 to 15
The CpG-ODN comprises any one nucleotide among SEQ ID NOs: 13 to 15.
The claims focus on a porous silica pore-loaded CpG-ODN-RNA conjugate architecture with pore diameter 7 to 30 nm, where the RNA is IDO siRNA defined by specific SEQ ID NO pair selections or SEQ ID NOs 11 and 12. Another independent claim further restricts the CpG-ODN component to nucleotides among SEQ ID NOs: 13 to 15, while preserving the same porous silica pore range.
Stated Advantages
Efficient IDO1 knockdown.
Suppression of kynurenine and Treg differentiation.
Increased Type I interferon.
Improved CD8/Treg ratio.
Sustained release/biodistribution.
Therapeutic efficacy, including synergy with checkpoint inhibitors.
Documented Applications
Anti-cancer use via intratumoral administration of the nucleic acid carrier in CT26 syngeneic mouse models.
Use in cancer treatment, including administration to a subject in need.
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