CN-121971656-A - Composition for targeting CXCL7 gene and application of composition in preparation of fungal keratitis medicines

Abstract

The invention provides a composition targeting CXCL7 gene and application thereof in preparation of drugs for fungal keratitis, and relates to the field of biological medicine. The composition is formed by transfection of a vector containing CXCL7 targeted interference sequences, and the CXCL7 targeted interference sequences are shown as SEQ ID No. 1. The vector is an adeno-associated viral vector, and the CXCL7 targeting interference sequence is inserted downstream of the U6 promoter of the adeno-associated viral vector. The CXCL7 is used as a new target point of the fungal keratitis, the expression of the CXCL7 is inhibited by a gene intervention means, the problems of excessive immune response and difficult control of inflammatory response are solved, accurate local treatment is realized by an AAV vector system, the excessive activation of the immune response can be effectively reduced, the excessive aggregation of immune cells is reduced, the secretion of inflammatory factors is reduced, the inflammatory response of cornea is reduced, and the cornea repair is facilitated.

Inventors

• GONG BO
• HE YU
• ZHANG DAN
• GUO XIAOXIN
• DONG JIE
• LI MINGZE
• WU WEIJIA

Assignees

• 四川省医学科学院·四川省人民医院

Dates

Publication Date

20260505

Application Date

20260409

Claims (5)

1. 1. The CXCL7 gene targeting composition is characterized by being transfected by a vector containing a CXCL7 targeting interference sequence, and the CXCL7 targeting interference sequence is shown as SEQ ID No. 1.
2. 2. A composition for targeting a CXCL7 gene according to claim 1, wherein said vector is an adeno-associated viral vector and said CXCL7 targeting interference sequence is inserted downstream of the U6 promoter of said adeno-associated viral vector.
3. 3. Use of a composition targeting CXCL7 gene according to claim 1 for the preparation of a medicament for fungal keratitis.
4. 4. The use according to claim 3, wherein the composition interferes with the immune response process in fungal keratitis by targeted inhibition of CXCL7 expression and enhances corneal tissue repair capacity.
5. 5. The use according to claim 4, wherein the medicament comprises one or more pharmaceutically acceptable carriers, excipients or diluents.

Description

Composition for targeting CXCL7 gene and application of composition in preparation of fungal keratitis medicines Technical Field The invention relates to the field of biological medicine, in particular to a CXCL7 gene targeting composition and application thereof in preparation of fungal keratitis medicines. Background Fungal keratitis (Fungal Keratitis, FK) is a serious blinding ocular surface disease caused by infection of cornea with pathogenic fungi, belongs to an important type of infectious keratitis, and is found in agricultural workers and people with history of ocular trauma. Current methods of treatment for FK rely mainly on antifungal drugs, such as natamycin and voriconazole, but these drugs often face significant limitations. First, antifungal drugs have a problem of poor permeability, and due to the limitation of the corneal barrier, the drugs are difficult to effectively permeate into the lesion area, resulting in an unsatisfactory therapeutic effect. Secondly, with the widespread use of antifungal drugs, part of the true strains gradually develop drug resistance, which makes the treatment difficult to work, and the treatment period is long, bringing great side effects and drug dependence to patients. In addition, existing drugs kill pathogens mainly through antifungal drugs, but these drugs cannot effectively regulate the overactivation of immune responses, resulting in the overrecruitment of immune cells and the excessive release of inflammatory factors, thereby exacerbating corneal damage. And most of the current treatments rely on the use of systemic drugs, which can lead to systemic immune responses or adverse side effects, and risk immune escape. The traditional systemic administration mode is difficult to realize local high-efficiency delivery of the medicine, so that the treatment effect cannot be concentrated at the focus part, and the treatment effect is affected. Therefore, a solution that can achieve accurate targeting on immune regulation and therapeutic effects, improve therapeutic effects of drugs and reduce side effects is needed to further solve the problems of excessive immune reaction, drug resistance and poor drug permeability of the traditional therapeutic methods. Disclosure of Invention The invention aims to provide a CXCL7 gene targeting composition and application thereof in preparation of drugs for fungal keratitis, CXCL7 is used as a new target point of fungal keratitis, CXCL7 expression is inhibited by a gene intervention means, the problems of excessive immune response and difficult control of inflammatory response are solved, accurate local treatment is realized by an AAV vector system, excessive activation of immune response can be effectively reduced, excessive aggregation of immune cells is reduced, secretion of inflammatory factors is reduced, and thus, corneal inflammatory response is reduced, and cornea repair is facilitated. The invention solves the technical problems by adopting the following technical scheme. In one aspect, the embodiments of the present application provide a composition targeting a CXCL7 gene, which is transfected with a vector comprising a CXCL7 targeting interfering sequence, wherein the CXCL7 targeting interfering sequence is shown in SEQ ID No. 1. Further, the vector is an adeno-associated viral vector, and the CXCL7 targeting interference sequence is inserted downstream of the U6 promoter of the adeno-associated viral vector. On the other hand, the embodiment of the invention also provides application of the CXCL7 gene-targeted composition in preparation of fungal keratitis treatment products. Further, the compositions interfere with the immune response process in fungal keratitis by targeted inhibition of CXCL7 expression and enhance corneal tissue repair. Further, the product contains one or more pharmaceutically acceptable carriers, excipients or diluents. Compared with the prior art, the embodiment of the invention has at least the following advantages or beneficial effects: 1. The CXCL7 is firstly provided as a therapeutic target of the fungal keratitis, and the accurate intervention is carried out by targeting the CXCL7 gene, so that the immune response is regulated, and the inflammatory response is reduced. Compared with the traditional antifungal drug treatment, the invention not only can reduce the cornea inflammation by controlling the immune response, but also can avoid the drug resistance problem of the antifungal drug; 2. The invention can effectively reduce excessive recruitment of immune cells, regulate release of inflammatory factors, promote cornea repair and avoid the problems of excessive immune reaction and poor drug permeability in the traditional drug treatment by means of gene intervention; 3. The composition provided by the invention can be combined with medicines, can accurately deliver gene inhibitors to focus positions by adopting a local injection mode, has higher targeting property and biocompatibility,