Preparation method and application of nucleic acid spherical nanoparticle medicine

A nanoparticle and nucleic acid technology, used in nanomedicine, drug combination, drug delivery, etc., can solve the problem of low delivery efficiency, and achieve the effect of not easy to degrade, good stability, and inhibition of translation

Active Publication Date: 2022-02-22
SUZHOU WEAST BIOTECHNOLOGY CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to provide nucleic acid spherical nanoparticle drugs for efficient cytoplasmic gene delivery, and solve the problem of low delivery efficiency in existing delivery methods

Method used

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  • Preparation method and application of nucleic acid spherical nanoparticle medicine
  • Preparation method and application of nucleic acid spherical nanoparticle medicine
  • Preparation method and application of nucleic acid spherical nanoparticle medicine

Examples

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Embodiment 1

[0046] Preparation method of DNA NPs-18 nt: Mix 500 nM DNA-18 nt and 45 μM disulfide monomer compound in 20 mM Tris-HCl buffer (pH = 7.5) at 37°C for 15 min. Subsequently, unreacted DNA and disulfide monomer compounds were removed by dialysis in water for 48 h to finally obtain DNA NPs-18 nt. The particle size of the DNA NPs-18nt synthesized in this example is about 50 nm. To optimize the assembly conditions, different concentrations of disulfide monomer compounds were added to Tris-HCl buffer (pH = 7.5) containing 5 μM DNA-18 nt (N / P = 1~15).

[0047] In Example 1, survivin mRNA was used as the target positive-sense RNA, wherein Random DNA, DNA-18 nt and its positive-sense RNA—survivin mRNA sequences are shown in Table 1.

[0048] The sequence list of DNA and sense RNA adopted in the embodiment and comparative example of table 1

[0049]

[0050] Note: The target sequence of the survivin probe is the NO.305-NO.321 base interval of survivin mRNA with a total length of 265...

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Abstract

The invention provides a method for preparing nucleic acid spherical nanoparticle medicine and its application. The nucleic acid spherical nanoparticle medicine is self-assembled from a disulfide monomer compound and a nucleic acid sequence complementary to a detection target sense nucleic acid sequence. The nucleic acid spherical nanoparticle drug can enter the cytoplasm through a non-endocytic pathway, and then be rapidly depolymerized by endogenous glutathione (GSH) in the cell, which promotes the decomposition of the nanoparticle and the release of nucleic acid for gene therapy, and then Inhibits the expression of tumor-associated genes.

Description

technical field [0001] The invention belongs to the field of biological gene therapy, in particular to a preparation method and application of nucleic acid spherical nanoparticle medicine. Background technique [0002] Gene therapy has broad application prospects for the treatment of various diseases such as cancer, genetic diseases and viral infections. Currently, many nucleic acid drugs are in clinical trials, and some drugs have been approved in the United States and Europe. Despite great progress, the commercial development of nucleic acid drugs still faces several challenges, such as enzymatic degradation, inefficient cytoplasmic delivery, rapid hepatic clearance, and nonspecific side effects. [0003] Successful gene therapy depends largely on the development of delivery vehicles with high transfection efficiency and low cytotoxicity. Both viral and non-viral vectors can be used to package nucleic acids and facilitate cellular uptake. Viral vectors are widely used f...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K48/00A61K31/7088A61K47/54A61P35/00
CPCA61K47/54A61K47/6929A61K31/7088A61P35/00B82Y5/00
Inventor 李娟孙丽芹周洁李婧影杨黄浩
Owner SUZHOU WEAST BIOTECHNOLOGY CO LTD
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