Sequence of scfv for inhibiting hiv-1 virus infection and application thereof

A technology for HIV-1 and virus infection, which is applied in antiviral agents, antiviral immunoglobulins, and targeting specific cell fusion, etc., and can solve problems such as high HIV-1 mutation rate

Active Publication Date: 2021-02-26
SHENZHEN CITY OF REGENERATION BIOLOGICAL PHARMA TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] But HIV-1 has a high mutation rate, resulting in escape clones

Method used

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  • Sequence of scfv for inhibiting hiv-1 virus infection and application thereof
  • Sequence of scfv for inhibiting hiv-1 virus infection and application thereof
  • Sequence of scfv for inhibiting hiv-1 virus infection and application thereof

Examples

Experimental program
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Effect test

Embodiment Construction

[0034] A first aspect of the present invention provides:

[0035] A scFv protein for inhibiting HIV-1 virus infection, the sequence of the scFv protein is shown in SEQ ID NO.1-SEQ ID NO.9.

[0036] A second aspect of the present invention provides:

[0037] A CAR molecule that inhibits HIV-1 virus infection, the CAR molecule includes an extracellular antigen-binding domain and an intracellular domain, the extracellular antigen-binding domain is a scFv protein, and the sequence of the scFv protein is as shown in SEQ ID NO. 1~shown in SEQ ID NO.9.

[0038] In some examples of CAR molecules, the sequence of the intracellular domain is shown in SEQ ID NO.10.

[0039] A third aspect of the present invention provides:

[0040] A CAR-T cell that suppresses HIV-1 virus infection, the CAR-T cell is transduced with at least one CAR molecule, the CAR molecule includes an extracellular antigen binding domain and an intracellular domain, and the extracellular antigen The binding domain...

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Abstract

The invention discloses a scFv sequence for inhibiting HIV-1 virus infection and application thereof. Based on the variable region heavy chain (V) of HIV-1 neutralizing antibody VRC01 H ) and light chain (V L ), using its own method to connect its sequences to form scFv, and a total of 9 scFv molecules with high affinity to gp120 protein of HIV-1 were obtained. The scFv sequences of some examples of the present invention have good affinity to HIV-1 virus, and can effectively inhibit the virus from infecting target cells TZM-bl cells. Using the scFv sequences of some examples of the present invention, CAR-T cells that can inhibit HIV-1 virus infection can be constructed, and the CAR-T cells can strongly mediate the lysis of target cells and release LDH. The CAR-T cells of some examples of the present invention can better avoid the escape caused by HIV-1 virus mutation by loading multiple CAR molecules with different scFv sequences, and have a wider-spectrum HIV-1 virus inhibitory effect.

Description

technical field [0001] The invention relates to the technical field of cellular immunotherapy, in particular to scFv sequences for inhibiting HIV-1 virus infection and applications thereof. Background technique [0002] After human immunodeficiency virus type 1 (Human Immunodificiency Virus Type-1, HIV-1) infection, combined antiretroviral therapy (combined antiretroviral therapy, cART) can effectively inhibit virus replication. However, since the virus integrates in the infected cells and forms a stable latent infection reservoir, once the infected person stops cART treatment, the viremia flares up again in a short time, which constitutes a major obstacle to cure HIV-1 infection . [0003] The current research focus is to activate the latently infected virus through specific latent infection reversing agents (latency-reversing agents, LRAs), and then drug treatment or induce the body's immune system to kill infected cells. This intervention strategy is known as "shock and...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K16/10C07K19/00C12N5/10A61K39/00A61P31/18
CPCA61P31/18A61K39/001102C07K14/7051C07K16/1045C07K2319/33
Inventor 张辉
Owner SHENZHEN CITY OF REGENERATION BIOLOGICAL PHARMA TECH CO LTD
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