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Microrna-based therapy targeted against lcp-1 positive cancers

A technology for LCP-1, cancer, applied in DNA/RNA fragments, recombinant DNA technology, stably introducing foreign DNA into chromosomes, etc.

Pending Publication Date: 2021-03-26
微核糖核苷酸治疗有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For liposomal delivery systems, the inefficiency in targeting tumors and delivering their therapeutic payloads in vivo has resulted in significant complications and side effects, as demonstrated in early clinical trials of the first miRNA-based therapeutics

Method used

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  • Microrna-based therapy targeted against lcp-1 positive cancers
  • Microrna-based therapy targeted against lcp-1 positive cancers
  • Microrna-based therapy targeted against lcp-1 positive cancers

Examples

Experimental program
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Embodiment approach

[0076] CLAIMS 1. A method of treating LCP-1 positive cancer patients by administering specific miRNA sequences, including miR-885-5p. MiRNA sequences can be embedded in delivery vectors loaded with or overexpressing specific miRNA sequences (including EVmiR TM complex) and have been found to affect cancer-associated proteins involved in cancer growth and metastasis.

[0077] 2. The method according to statement 1, wherein a set of miRNAs corresponds to miR-16-5p, miR-23a-5p, miR-125b-5p, miR-145-5p, miR-146a-3p, miR-181c-5p, miR-218-5p, miR-495-3p, let-7b-5p, miR-30a-5p, miR-30b-5p, miR-30c-5p, miR-30d-5p, miR-30e-5p, miR- 194-5p, miR-302a-3p, miR-302a-5p, miR-335-3p, miR-335-5p, miR-367-3p, miR-373-3p, miR-885-5p (see miRNA group, Table 1).

[0078] 3. The method according to statement 1, wherein the delivery vehicle is an extracellular vesicle (EV) or microvesicle derived from umbilical cord stem cells (including umbilical cord glial cells), blood, umbilical cord blood, o...

Embodiment

[0115] In vitro studies evaluating cancer cell response to EV-mediated miRNA therapy: breast (MDA-MB-231&MCF-7), colon (RKO, HT-29, CACO2) and ovarian (SKOV3, EFO-21) adenocarcinoma, Prostate cancer (LNCaP) and acute monocytic leukemia (THP-1) cell lines were exposed to EVs containing exogenous therapeutic miR-885-5p (along with endogenous miRNA panel, see Table 2). Response to treatment was assessed by cell morphology, proliferation, migration, gene expression, and apoptosis assays ( image 3 and 4 ). Our in vitro experiments confirmed that stem cell-derived EVs are internalized by multiple cancer cell lines and induce biological effects as evidenced by membrane damage, cell shrinkage, and blebbing of target cells ( Figure 5 ). Importantly, there is evidence that EVs induce apoptosis, inhibit cell proliferation, and attenuate tumor growth and metastasis in a dose / time-dependent manner. The pro-apoptotic and anti-migratory effects of EVs in cancer cells were almost comple...

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Abstract

The present invention relates to a panel of miRNAs comprising miR-16-5p, miR-23a-5p, miR-125b-5p, miR-145-5p, miR-146a-3p, miR-181c-5p, miR-218-5p, miR-495-3p, let-7b-5p, and further comprising one ormore miRNAs selected from the group consisting of miR-30a-5p, miR-30b-5p, miR-30c-5p, miR-30d-5p, miR-30e-5p, miR-194-5p, miR-302a-3p, miR-302a-5p, miR-335-3p, miR-335-5p, miR-367- 3p, miR-373-3p, and miR-885-5p, and to extracellular vesicles (EVs), e.g. of stem cell origin, loaded with the panel of miRNAs. The present invention further provides the panel or EVs for use in a method of treating LCP-1 positive cancer in a patient.

Description

technical field [0001] The present invention relates to new technologies using miRNAs and their ability to target and downregulate oncoprotein activity in LCP-1 positive cancers. This technology is designed to deliver specific miRNA inhibitor sequences encapsulated in biological or synthetic vesicles that will affect a panel of genes and proteins (including LCP1 / LCP-1) associated with cancer initiation, growth, invasiveness and metastasis expression. Background technique [0002] Cancer is a heterogeneous disease with a cellular hierarchy and many distinct phenotypes, with a high capacity for tumor spread and metastasis. Progression to the metastatic stage presents the greatest challenge to effective cancer treatment and is responsible for most cancer-related deaths. The invasion-metastasis cascade is a multistep cellular process involving the spread of cancer cells through the surrounding extracellular matrix, survival in circulation and initial seeding, followed by subse...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/113A61K31/7105A61K9/50
CPCA61K31/7105C12N15/1135C12N2310/141A61P35/00C12N15/90C12Q1/68C12Q2600/158A61K45/06
Inventor 玛丽安娜·普罗科皮
Owner 微核糖核苷酸治疗有限公司
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