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Self-assembled DNA tetrahedron and peptide vaccine delivery system

A delivery system and self-assembly technology, applied in the field of biomedicine, can solve the problems of limited T cell activation ability and low immunogenicity, and achieve the effects of excellent biocompatibility, shortened time and difficulty, and high biological stability

Pending Publication Date: 2022-03-15
CHINA PHARM UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, studies have found that most neoantigens have low immunogenicity and limited ability to activate T cells

Method used

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  • Self-assembled DNA tetrahedron and peptide vaccine delivery system
  • Self-assembled DNA tetrahedron and peptide vaccine delivery system
  • Self-assembled DNA tetrahedron and peptide vaccine delivery system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] The self-assembled DNA tetrahedron used is composed of four single-stranded DNAs, the sequence of the first single-stranded DNA is shown in SEQ ID NO:10, the sequence of the second single-stranded DNA is shown in SEQ ID NO:11, and the third The sequence of the single-stranded DNA is shown in SEQ ID NO:12, and the sequence of the fourth single-stranded DNA is shown in SEQ ID NO:13.

[0056] The recombinant self-assembled DNA tetrahedron is constructed on the basis of the self-assembled DNA tetrahedron, as follows:

[0057] In one aspect, the CpG ODN motif shown in SEQ ID NO: 1 is selected as the built-in motif adjuvant.

[0058] On the other hand, first select the sequence SEQ ID NO: 10 of the first single-stranded DNA as a built-in motif adjuvant, select the first base at the 5' end as the starting position in the sequence of the single-stranded DNA, and start from From the starting position, the sequence of the single-stranded DNA is replaced by the sequence of the Cp...

Embodiment 2

[0066] This example is to verify the successful implementation effect of self-assembly.

[0067] Select chains 1 to 4 from Example 1 to prepare DNA tetrahedrons loaded with polypeptides. The main steps are:

[0068] (1) The No. 1 to No. 4 chains in Example 1 whose C-terminus was not modified were selected, chemically synthesized, and dissolved in PBS (pH=7.0). Among them, No. 1 chain is recorded as DCP-A.

[0069] (2) The NitraTh peptide whose N-terminus is modified with maleimide propionic acid (this peptide is the auxiliary epitope peptide, the sequence is SEQ ID NO: 18) was dissolved in PBS (PH=7.0).

[0070] Take the dissolved chains 1 to 4 and NitraTh peptide with equimolar mass, and rotate and mix them at 37°C for 2 hours, so that each single-stranded DNA can be fully coupled with the polypeptide to form 4 complexes. Among them, the complex of No. 1 chain and NitraTh peptide is recorded as DCP-A-NitraTh.

[0071] (3) Afterwards, the four complexes are mixed together, ...

Embodiment 3

[0077] This example is to verify the residency of DNA tetrahedral lymph nodes.

[0078] (1) Using chains 1 to 4 of Example 1, replace the peptide with FITC-labeled SIINFEK according to the steps of Example 2 (FITC) L-peptide, prepared to load SIINFEK (FITC) The DNA tetrahedron of the L peptide (named DCP-SIINFEK (FITC) L), according to 16nmol / 200uL / mouse, inject subcutaneously into mouse groin, each 100uL on the left and right sides.

[0079] The amino acid sequence of the SIINFEKL peptide is: H-Ser-Ile-Ile-Asn-Phe-Glu-Lys-Leu-OH. This peptide is an MHC-I Kb restricted epitope peptide derived from OVA protein, which can effectively activate CD8+ T cells and is widely used as a model antigen peptide.

[0080] (2) After 24 hours, the mice were sacrificed, the iliac lymph nodes of the mice were peeled off, and tissue fluorescence photographs were taken.

[0081] The result is as Figure 4 As shown, compared with the blank control group and pure SIINFEK (FITC) Compared with ...

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Abstract

The invention relates to a self-assembled DNA tetrahedron and a peptide vaccine delivery system. And the self-assembled DNA tetrahedron is composed of four single-stranded DNAs. The recombinant self-assembled DNA tetrahedron is obtained by recombining a self-assembled DNA tetrahedron. According to the peptide vaccine delivery system, a recombinant self-assembly DNA tetrahedron serves as a main body, and the 5'end or the 3 'end of each single-stranded DNA of the main body is coupled with helper epitope peptide or peptide vaccine.By means of the delivery system, the vaccines can efficiently reside in lymph nodes and are taken and presented by DC cells, so that antigen-specific T cells are effectively activated, and tumor growth is inhibited.

Description

technical field [0001] The invention relates to a self-assembled DNA tetrahedron and a peptide vaccine delivery system, belonging to the technical field of biomedicine. Background technique [0002] With the development of tumor immunology, bioinformatics and high-throughput sequencing technology, tumor somatic mutations and frameshift mutations have been identified, and a class of neoantigens that do not occur in healthy cells and only exist in tumors have been discovered. the tumor neoantigen. Therefore, tumor neoantigens are not subject to central immune tolerance and have good targeting. These unique properties make neoantigens excellent candidates for vaccines against cancer. However, studies have found that most neoantigens have low immunogenicity and limited ability to activate T cells. Therefore, there is a great need to develop a method that can enhance neoantigens to generate effective and durable tumor immune responses. [0003] To improve the immune response ...

Claims

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Application Information

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IPC IPC(8): C12N15/11A61K39/00A61K39/39A61K47/26A61P35/00
CPCC12N15/11A61K39/0011A61K39/39A61K47/26A61P35/00C12N2310/151A61K2039/55561
Inventor 姚文兵田浤康彦良高向东张莉张万里
Owner CHINA PHARM UNIV
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