Small nucleic acid for inhibiting human cytomegalovirus infection as well as preparation and application thereof

A technology of human cytomegalovirus and small nucleic acid, which is applied in the field of small nucleic acid and its preparation and application to inhibit human cytomegalovirus infection, and can solve problems such as inability to respond quickly, lack of selective delivery of infected cells, and poor carrier stability , to achieve the effect of improving drug effect, improving therapeutic effect and reducing toxicity

Pending Publication Date: 2021-01-05
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the shortcomings of the prior art, such as many adverse reactions, drug resistance, lack of selective delivery to infected cells, poor carrier stability, and...

Method used

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  • Small nucleic acid for inhibiting human cytomegalovirus infection as well as preparation and application thereof
  • Small nucleic acid for inhibiting human cytomegalovirus infection as well as preparation and application thereof
  • Small nucleic acid for inhibiting human cytomegalovirus infection as well as preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] Example 1 Screening of siRNA

[0062] For HCMV virus early protein (Immediate early protein) IE1 protein (HCMV IE1:>sp|P03169|VIE1_HCMVT 55kDa immediate-early protein 1OS=Human cytomegalovirus (strain Towne) OX=10363GN=UL123 PE=1SV=1; Link: https: / / www.uniprot.org / uniprot / P03169) (SEQ ID NO.5) and IE2 protein (HCMV IE2:>tr|Q6SWJ2|Q6SWJ2_HCMVORegulatory protein IE2 OS=Human cytomegalovirus (strain Toledo) OX=311339GN=UL122 PE=4SV =1; Link: https: / / www.uniprot.org / uniprot / Q6SWJ2) (SEQ ID NO.6) mRNA expressed, a small nucleic acid is designed, which can bind to mRNA with high specificity and block the expression of related proteins Expression, and then achieve the therapeutic effect of inhibiting virus replication; at the same time, in order to reduce the off-target effect, according to the existing literature reports (reference 1: Hamilton S T, Jens M, Manfred M, et al. Human Cytomegalovirus Replication Is Strictly Inhibited by siRNAs Targeting UL54, UL97 or UL122 / 123 G...

Embodiment 2

[0070] Example 2 Synthesis of block polymers and preparation of nanoparticles

[0071] Mix the scRNA and siRNA (siRNA-1, siRNA-2) in Example 1 at a molar ratio of 1:1:1, and then prepare nanoparticles. The prepared nanoparticles have a "nuclear-membrane" structure and can be independently Packed as a nanoscale nucleic acid carrier; wherein, the core material synthesis involved, the surface material synthesis method, and the nanoparticle preparation method are as described in the references (Feng J, ChenS, Ge X, et al.Precise Assembly of Synthetic Carriers of siRNA through a Series of Interlocked Thermodynamically Self-Regulated Processes[J].Advanced Functional Materials,2017,28(6):1703207.).

[0072] The core material is networked cationic polymer, and the surface material is polyethylene glycol-polycaprolactone-carboxy-modified maltotriose block polymer PEG-PCL-Maltotriose-COOH (including five Fluorophenol-modified polyethylene glycol block polymer PFP-PEG-PCL-Maltotriose-CO...

Embodiment 3

[0077] The effect of embodiment 3 targeting molecules

[0078] (1) Link targeting group

[0079] Through the formulation method, we link the targeting molecule CX that can specifically recognize HCMV-infected cells through chemical covalent bonds 3 CL 1 , the polypeptide sequence was obtained by solid-phase synthesis, and its sequence was: QHHGV-TKCNITCSKMTSKIPVALLIHYQQNQAS-CGKRAIILETRQHRLACADPKEQWVKDAMQHLDRQAAALTRNG (SEQ ID NO.4), and Fmoc protection was carried out to the biologically active end (the polypeptide was synthesized by Shanghai Jier Polypeptide Company), and lysine was connected to one end of the polypeptide The amino group of the acid is chemically linked with the pentafluorophenol in the polymer material forming nanoparticles, and the specific steps are:

[0080] ① Get 15mg block polymer PFP-PEG45-PCL-Maltotriose-COOH (i.e. the polyethylene glycol-polycaprolactone-carboxyl modified maltotriose block polymer in Example 2) (2.5mmoL), then add Equimolar CX 3 C...

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Abstract

The invention discloses small nucleic acid for inhibiting human cytomegalovirus infection as well as a preparation and application thereof. The small nucleic acid for inhibiting human cytomegalovirusinfection has nucleotide sequences as shown in SEQ ID NO.1-3. According to the invention, the small nucleic acid is mainly used as a therapeutic drug to prevent further expression of related proteinsof HCMV-related genes, and meanwhile, targeting molecules capable of being combined with the small nucleic acid are designed for surface characteristics of virus-infected cells to improve the phagocytic efficiency of an action site of the small nucleic acid, so that the treatment concentration of the lesion action site is improved, the treatment effect is enhanced, meanwhile the uptake rate of thenon-target tissue is reduced to reduce the potential toxicity, and an effective solution is provided for HCMV infection in-vivo treatment.

Description

technical field [0001] The invention relates to the field of biology, in particular to a small nucleic acid for inhibiting human cytomegalovirus infection, its preparation and application. Background technique [0002] Human cytomegalovirus (HCMV), also known as cellular inclusion body virus, is the largest DNA herpes virus known, due to the swelling of infected cells and huge nuclear inclusion bodies, belonging to the β-herpesvirus subfamily. It is a widely disseminated opportunistic virion and an important teratogenic and neurologically damaging pathogen in humans. HCMV infection is very common in the natural population, and the infection rate in the population is relatively high, and the infection rate in developed countries is 30-70%. [0003] The first HCMV infection mostly occurs in infants and young children. Once HCMV invades the human body, it will exist in the body for a long time or for life. For the vast majority of individuals with normal immune function, it o...

Claims

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Application Information

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IPC IPC(8): C12N15/113B82Y40/00B82Y5/00A61K9/14A61K47/34A61K47/42A61K31/7105A61K48/00A61P31/22
CPCC12N15/1133B82Y40/00B82Y5/00A61K9/146A61K31/7105A61P31/22C12N2310/141
Inventor 陈俊朱桦葛雪梅刘小莲
Owner JINAN UNIVERSITY
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