WO2022077727A1 - Application de chaf1a en tant que cible d'activation pour une infection par le vih-1 latent - Google Patents

Application de chaf1a en tant que cible d'activation pour une infection par le vih-1 latent Download PDF

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WO2022077727A1
WO2022077727A1 PCT/CN2020/133163 CN2020133163W WO2022077727A1 WO 2022077727 A1 WO2022077727 A1 WO 2022077727A1 CN 2020133163 W CN2020133163 W CN 2020133163W WO 2022077727 A1 WO2022077727 A1 WO 2022077727A1
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hiv
chaf1a
latent
latent infection
infection
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PCT/CN2020/133163
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张辉
马显才
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中山大学
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
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    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
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    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
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    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844—Nucleic acid amplification reactions
    • C12Q1/6851—Quantitative amplification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/70—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
    • C12Q1/701—Specific hybridization probes
    • C12Q1/702—Specific hybridization probes for retroviruses
    • C12Q1/703—Viruses associated with AIDS
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • C—CHEMISTRY; METALLURGY
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    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
    • C12N2740/15041—Use of virus, viral particle or viral elements as a vector
    • C12N2740/15043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
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    • C12N2800/00—Nucleic acids vectors
    • C12N2800/10—Plasmid DNA
    • C12N2800/106—Plasmid DNA for vertebrates
    • C12N2800/107—Plasmid DNA for vertebrates for mammalian
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N2015/1006—Investigating individual particles for cytology

Definitions

  • the invention relates to the technical field of HIV-1 virus, and more particularly, to the application of CHAF1A as an activation target of HIV-1 latent infection.
  • HIV-1 The fundamental reason why HIV-1/AIDS cannot be completely cured so far is the latent infection of HIV-1, that is, HIV-1 is temporarily silenced in host cells, especially CD4 + T cells, and reactivated with cell activation .
  • cART combined antiretroviral therapy
  • this treatment method is not thorough and cannot permanently remove the virus, so patients must take medicine for life.
  • Completely removing the virus from the human body has become a major difficulty in curing HIV-1/AIDS.
  • scientists have successively proposed a variety of new treatment strategies, including functional cures such as "shock and kill", "block and lock”, which aim to not completely eradicate HIV-1 and achieve HIV-1/AIDS withdrawal. The medicine does not bounce back to the target.
  • HIV-1 latent infection is mediated by the following aspects: HIV-1 integration into some gene introns prone to clonal expansion and transient expression; loss of host and viral transcriptional facilitators and transcriptional repressors enrichment for repressive epigenetic modification proteins read and write inhibitory epigenetic modifications near the HIV-1 promoter, and activating epigenetic modifications are removed by specific proteins; noncoding RNA-mediated post-transcriptional control, etc.
  • HIV-1 latent infection can be reactivated, thereby killing infected cells. This method of first activation and then removal is the "shock and kill" functional therapeutic strategy.
  • the chromatin assembly protein CAF-1 (chromatin assembly factor 1) consists of three main subunits: CHAF1A, CHAF1B and RBBP4.
  • CHAF1A is the most important subunit of CAF-1.
  • CHAF1A can not only present newly synthesized histones H3-H4 near the replicating DNA replication fork, but also recruit numerous epigenetic modifiers to mediate transcriptional repression of endogenous retroviruses.
  • CHAF1A can suppress the expression of latent HIV-1 in human adult cells such as human primary CD4 + T cells. At present, there is no report of drugs targeting CHAF1A to activate HIV-1 latent infection.
  • the purpose of the present invention is to provide a method for separating high-purity bovine serum albumin from bovine serum in order to overcome the deficiencies of the prior art.
  • the first object of the present invention is to provide the application of CHAF1A as an activation target of HIV-1 latent infection.
  • the second object of the present invention is to provide the application of CHAF1A in screening HIV-1 latent infection activators.
  • the third object of the present invention is to provide the application of the substance inhibiting or knocking out CHAF1A in the preparation of HIV-1 latent infection activator.
  • the fourth object of the present invention is to provide an HIV-1 latent infection activator.
  • the fifth object of the present invention is to provide the use of a substance that inhibits or knocks out CHAF1A in the preparation of a medicament for delaying HIV-1-infected cells from entering a state of latent infection.
  • the sixth object of the present invention is to provide the use of a substance that inhibits or knocks out CHAF1A in the preparation of a drug for improving the genetic diversity of the activated virus.
  • the seventh object of the present invention is to provide an application of a substance that inhibits or knocks out CHAF1A in the preparation of a drug for increasing the content of viral RNA.
  • the eighth object of the present invention is to provide the application of the HIV-1 latent infection activator in the preparation of a medicine for increasing the content of viral RNA.
  • the present invention finds that the three subunits CHAF1A, CHAF1B and RBBP4 of chromatin assembly factor can mediate the inhibition of HIV-1 expression, among which CHAF1A, the largest subunit of CAF-1, can significantly suppress the expression of HIV-1 and promote HIV-1 latent infection.
  • CHAF1A the largest subunit of CAF-1
  • the removal of CHAF1A can make latent HIV-1 express again, and activate the viral latent pool superimposed with conventional latent infection activators TNF ⁇ , SAHA, JQ-1, etc.
  • the present invention therefore claims the use of CHAF1A as an activation target for HIV-1 latent infection.
  • CHAF1A in screening HIV-1 latent infection activators is also claimed, and substances that inhibit or knock out CHAF1A have the effect of HIV-1 latent infection activators.
  • the present invention claims the use of substances that inhibit or knock out CHAF1A in the preparation of HIV-1 latent infection activators.
  • the Act also claims an activator of HIV-1 latent infection, including a substance that inhibits or knocks out CHAF1A.
  • the substance that inhibits or knocks down CHAF1A is siRNA, and liposome transfection of siRNA is used to target and knock out endogenous CHAF1A.
  • the siRNA is one or more of 5'-GCACAGTCATCATTGATTT-3', 5'-CCATAAGGTCCGCCAGAAA-3', and 5'-GCAGGACAGTTGGAGTGAA-3'.
  • the substance that inhibits or knocks out CHAF1A is sgRNA.
  • the sgRNA is 5'-CACCGCTCGGGCCACTCGTCAGCTC-3'.
  • TNF ⁇ Preferably, one or more of TNF ⁇ , SAHA, or JQ-1 is also included.
  • SAHA is also included.
  • the application includes substances that inhibit or knock out CHAF1A, and one or more HIV-1 latent infection activators among TNF ⁇ , SAHA, or JQ-1 in the preparation of a drug for increasing the content of viral RNA.
  • the present invention has the following beneficial effects:
  • the present invention finds that the largest subunit CHAF1A of the chromatin assembly factor CAF-1 can significantly suppress the expression of HIV-1 and promote the latent infection of HIV-1.
  • the removal of CHAF1A can make latent HIV-1 express again, and can activate the virus latent pool by stacking with conventional latent infection activators TNF ⁇ , SAHA, JQ-1, etc.
  • the development of new latent infection activating drugs targeting CHAF1A is expected to more fully activate the latent virus and kill it by the human immune system, thereby reducing or even clearing the latent virus reservoir in the patient.
  • Figure 1 shows the reactivation of HIV-1 expression in the HIV-1 expressing cell line TZM-bl after knockdown of three CAF-1 subunits CHAF1A, CHAF1B and RBBP4 with siRNA.
  • Figure 2 shows the reactivation of virus by knockout of CHAF1A in latently infected cell lines.
  • Figure 3 shows the delayed effect of CHAF1A knockdown on HIV-1-infected CD4+ T cells entering latency.
  • Figure 4 shows the genetic diversity index of HIV-1 viral RNA activated by the knockout of CHAF1A.
  • Figure 5 shows the activation of latent virus by knockout of CHAF1A in clinical samples of HIV-1 infected patients.
  • test methods used in the following examples are conventional methods unless otherwise specified; the materials, reagents, etc. used are commercially available reagents and materials unless otherwise specified.
  • the HIV-1 expressing cell line infected with TZM-bl was evenly spread in a 24-well plate, and the culture conditions were: in DMEM, 10% FBS, 1% double antibody, 37°C, 5% CO 2 for 24 hours ;
  • siRNA was transfected into each well with liposomes to target and knock out endogenous CHAF1A, CHAF1B and RBBP4 respectively to inhibit their expression;
  • siRNAs targeting CHAF1A there are three siRNAs targeting CHAF1A, which are transferred to one well:
  • siRNAs targeting RBBP4 There are three siRNAs targeting RBBP4, co-transferred to one well:
  • Example 2 The promoting effect of CHAF1A on HIV-1 latent infection
  • sgRNA sequence: 5'-CACCGCTCGGGCCACTCGTCAGCTC-3'
  • sgNT sequence: 5'-ACGGAGGCTAAGCGTCGCAA -3'
  • the sgNT and sgCHAF1A targeted knockout J-Lat 10.6 cell lines with good growth status were evenly plated in 96-well plates, and the two groups were treated with the latent infection activator tumor necrosis factor ⁇ (TNF ⁇ ), vorinostat (SAHA) and triphenylmethane triisocyanate (JQ-1) treatment;
  • TNF ⁇ latent infection activator tumor necrosis factor ⁇
  • SAHA vorinostat
  • JQ-1 triphenylmethane triisocyanate
  • the latent infection cell line J-Lat 10.6 contains an integrated deficient HIV-1 genome, the pseudovirus does not re-amplify to generate new virus particles, and green fluorescent protein is fused to the Nef position of the model HIV-1 virus protein Therefore, the expression of GFP reflects the expression of HIV-1 pseudovirus, that is, the percentage of GFP expression represents the proportion of activated HIV-1 pseudovirus.
  • shluc and shCHAF1A lentiviruses In this part of the experiment, the lentiviral backbone pLKO.3G-RFP was used as the plasmid template to construct the corresponding targeted gene lentivirus.
  • the expression of RFP in the vector can indicate the infection efficiency of cells, and is determined by CMV. Promoter-driven, sustainable expression; U6 promoter drives shRNA to express the interfering RNA part.
  • the control shRNA is shluc, which is a shRNA targeting firefly luciferase.
  • shRNA in the experimental group is shCHAF1A, which is a shRNA targeting the mRNA coding region of the human CHAF1A gene, which can specifically interfere with the expression of endogenous CHAF1A and reduce the expression of CHAF1A.
  • the packaging system is as follows: 3 ⁇ g of VSVG, 6 ⁇ g of psPAX2, and 6 ⁇ g of shluc backbone were transfected into HEK293T cells of 10cm dish with lipo2000 for the production of shluc lentivirus; 3 ⁇ g of VSVG, 6 ⁇ g of psPAX2, and 6 ⁇ g of shCHAF1A
  • the backbone was transfected into 10cm dish HEK293T cells with lipo2000 for the production of shCHAF1A lentivirus; 48h after transfection, the supernatant was transferred to a new 50ml tube, and the cell residues were removed by centrifugation.
  • the obtained supernatants were shluc and shCHAF1A lentivirus;
  • CD4 + T cells were isolated from healthy human peripheral blood mononuclear cell PBMC, and co-incubated with phytohemagglutinin (PHA) and CD4 + T cells, through the activation of TCR signaling pathway to activate cells;
  • PHA phytohemagglutinin
  • the cells were divided into two groups and infected with shluc (target sequence: 5'-ACCGCCTGAAGTCTCTGATTAA-3') and shCHAF1A (target sequence: 5'-CCGACTCAATTCCTGTGTAAA-3') lentivirus, where shluc was the control group and shCHAF1A was the control group.
  • shluc target sequence: 5'-ACCGCCTGAAGTCTCTGATTAA-3'
  • shCHAF1A target sequence: 5'-CCGACTCAATTCCTGTGTAAA-3'
  • the viral RNA in each group was reverse transcribed into cDNA with HIV-1 specific reverse primer and cloned into T vector, and the sequence diversity of HIV-1 viral RNA in each group was determined by single-genome sequencing method. The standard sequence is used to calculate the genetic diversity index of each group of samples;
  • the viral RNA in each group was reverse transcribed into cDNA, and the viral RNA in each group of cDNA was subjected to fluorescence quantitative PCR with HIV-1 specific primers to determine the viral RNA content under the treatment of each group.

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Abstract

L'invention concerne une application de CHAF1A en tant que cible d'activation pour une infection par le VIH-1 latent. La sous-unité la plus grande du facteur d'assemblage de la chromatine CAF-1, CHAF1A, peut réprimer de manière significative l'expression du VIH-1 et favoriser l'infection par le VIH-1 latent. L'élimination de CHAF1A permet la réexpression du VIH-1 latent et, en outre, en superposition avec des activateurs d'infection latente classiques tels que TNFα, SAHA et JQ-1, permet d'activer le réservoir latent viral. Avec le développement de médicaments activant une infection latente ciblant CHAF1A, il est attendu que le virus latent soit plus complètement activé et qu'il soit tué à l'aide du système immunitaire humain, ce qui permet de réduire le réservoir latent du virus dans le corps d'un patient ou même de le retirer.
PCT/CN2020/133163 2020-10-16 2020-12-01 Application de chaf1a en tant que cible d'activation pour une infection par le vih-1 latent WO2022077727A1 (fr)

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Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106176753A (zh) * 2016-07-15 2016-12-07 南方医科大学 Rvx‑208作为hiv‑1潜伏感染逆转剂的应用
CN107596372A (zh) * 2017-08-29 2018-01-19 中山大学 Cbx4作为hiv‑1潜伏感染激活靶点的应用
WO2018081197A1 (fr) * 2016-10-27 2018-05-03 The University Of North Carolina At Chapel Hill Modulation d'interférons de type i pour réactiver le réservoir du vih -1 et améliorer le traitement du vih -1
WO2018089592A1 (fr) * 2016-11-09 2018-05-17 Washington University Compositions et méthodes pour traiter la latence du vih-1
CN108704135A (zh) * 2018-05-24 2018-10-26 江苏大学附属医院 Chaf1a抑制剂在制备胃癌治疗药物中的用途
CN109620954A (zh) * 2019-02-14 2019-04-16 武汉科技大学 一种激活潜伏hiv病毒的组合物及其应用
CN110475567A (zh) * 2017-03-31 2019-11-19 勃林格殷格翰国际有限公司 抗癌组合疗法
CN111110848A (zh) * 2019-11-18 2020-05-08 中山大学 Piwil4作为激活hiv-1潜伏感染的药物的靶点的应用
CN111544429A (zh) * 2020-06-24 2020-08-18 中国科学院广州生物医药与健康研究院 化合物6-bio在制备hiv潜伏感染病毒激活剂及在制备根除该病毒的药物中的应用

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013074794A1 (fr) * 2011-11-15 2013-05-23 The Uab Research Foundation Réactivation d'un virus de l'immunodéficience humaine latent

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106176753A (zh) * 2016-07-15 2016-12-07 南方医科大学 Rvx‑208作为hiv‑1潜伏感染逆转剂的应用
WO2018081197A1 (fr) * 2016-10-27 2018-05-03 The University Of North Carolina At Chapel Hill Modulation d'interférons de type i pour réactiver le réservoir du vih -1 et améliorer le traitement du vih -1
WO2018089592A1 (fr) * 2016-11-09 2018-05-17 Washington University Compositions et méthodes pour traiter la latence du vih-1
CN110475567A (zh) * 2017-03-31 2019-11-19 勃林格殷格翰国际有限公司 抗癌组合疗法
CN107596372A (zh) * 2017-08-29 2018-01-19 中山大学 Cbx4作为hiv‑1潜伏感染激活靶点的应用
CN108704135A (zh) * 2018-05-24 2018-10-26 江苏大学附属医院 Chaf1a抑制剂在制备胃癌治疗药物中的用途
CN109620954A (zh) * 2019-02-14 2019-04-16 武汉科技大学 一种激活潜伏hiv病毒的组合物及其应用
CN111110848A (zh) * 2019-11-18 2020-05-08 中山大学 Piwil4作为激活hiv-1潜伏感染的药物的靶点的应用
CN111544429A (zh) * 2020-06-24 2020-08-18 中国科学院广州生物医药与健康研究院 化合物6-bio在制备hiv潜伏感染病毒激活剂及在制备根除该病毒的药物中的应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SHERAZ KHAN;MAZHAR IQBAL;MUHAMMAD TARIQ;SHAHIDM. BAIG;WASIM ABBAS: "Epigenetic regulation of HIV-1 latency: focus on polycomb group (PcG) proteins", CLINICAL EPIGENETICS, BIOMED CENTRAL LTD, LONDON, UK, vol. 10, no. 1, 5 February 2018 (2018-02-05), London, UK, pages 1 - 19, XP021253267, ISSN: 1868-7075, DOI: 10.1186/s13148-018-0441-z *

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