Compositions and methods for inhibiting expression of the lect2 gene

a technology of lect2 and expression inhibition, applied in the direction of drug composition, dermatological disorder, nervous disorder, etc., can solve the problems of limited treatment options and need for lect2 amyloidosis treatment, and achieve the effect of preventing at least one symptom, and reducing lect2 gene expression

Inactive Publication Date: 2021-04-01
ALNYLAM PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0046]In yet another aspect, the present invention provides methods of preventing at least one symptom in a subject having a disease or disorder that would benefit from reduction in LECT2 gene expression. The methods include administering to the subject a prophylactically effective amount of the agent of the invention or a pharmaceutical composition of the invention, thereby preventing at least one symptom in the subject having a disorder that would benefit from reduction in LECT2 gene expression.
[0047]In one embodiment, the administration of the antisense polynucleotide agent to the subject causes a decrease in amyloid deposition (e.g., by preventing amyloid deposition or reducing amyloid deposition, e.g., by reducing size, number, or extent of amyloid deposits) or symptoms associated with amyloid deposition and / or a decrease in LECT2 protein levels.
[0059]In some embodiments, the second therapy is a non-antisense polynucleotide therapeutic agent that is effective to treat the disorder or symptoms of the disorder.

Problems solved by technology

Treatments for LECT2 amyloidosis are limited, and new treatments are needed.

Method used

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  • Compositions and methods for inhibiting expression of the lect2 gene
  • Compositions and methods for inhibiting expression of the lect2 gene
  • Compositions and methods for inhibiting expression of the lect2 gene

Examples

Experimental program
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Effect test

example 1

Antisense Synthesis

[0524]The antisense polynucleotides targeting LECT2 were synthesized using standard synthesis methods known in the art.

[0525]A detailed list of modified and unmodified antisense molecules targeting LECT2 is shown in Table 3, including the starting position and mRNA sequence of the antisense oligonucleotide relative to SEQ ID NO: 1.

example 2

In vitro Screening

[0526]In vitro screening of the antisense polynucleotides was performed by transfecting human primary hepatocytes with a single 500 nM dose of an antisense LECT2 polynucleotide using methods known in the art. 32000 cells / well in a 96 well plate were transfected for 24 hours in 0.4 μl RNAiMAX / well. A single dose transfection screen in cells transfected with the indicated antisense polynucleotide is shown in Table 4. The relative LECT2 mRNA expression relative to a mock transfected control was determined.

TABLE 2Abbreviations of nucleotide monomers used in nucleicacid sequence representation. It will be understoodthat these monomers, when present in an oligonucleotide,are mutually linked by 5′-3′-phosphodiester bonds.AbbreviationNucleotide(s)AAdenosine-3′-phosphateAf2′-fluoroadenosine-3′-phosphateAfs2′-fluoroadenosine-3′-phosphorothioateAsadenosine-3′-phosphorothioatea2′-O-methyladenosine-3′-phosphateas2′-O-methyladenosine-3′-phosphorothioateCcytidine-3′-phosphatedA2′...

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Abstract

The invention relates to antisense polynucleotide agents targeting the LECT2 gene, and methods of using such anti sense polynucleotide agents to inhibit expression of LECT2 and to treat subjects having a LECT2-associated disease, e.g., amyloidosis.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. application Ser. No. 15 / 564,288, filed Oct. 4, 2017, which is a U.S. National Stage Application under 35 U.S.C. § 371 of International Application No. PCT / US2016 / 026676, filed Apr. 8, 2016, which claims the benefit of U.S. Provisional Application No. 62 / 144,695, filed Apr. 8, 2015, the contents of which are hereby incorporated by reference in their entirety.SEQUENCE LISTING[0002]The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on April 6, 2016, is named A2038-7221WO_SL.txt and is 96,680 bytes in size.FIELD OF THE INVENTION[0003]The invention relates to the specific inhibition of the expression of the LECT2 gene.BACKGROUND OF THE INVENTION[0004]Amyloidosis is a group of diseases characterized by deposition of insoluble fibrous protein aggregates, called amylo...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12N15/113A61P25/28A61P17/00A61K31/712A61K31/7125A61K47/26
CPCC12N15/1136A61P25/28A61P17/00A61P1/16A61K31/7125A61K47/26A61K31/712C12N2310/11C12N2310/315C12N2310/351C12N2310/322C12N2310/3533C12N2310/335C12N2310/3521C12N2310/321
Inventor HINKLE, GREGORY
Owner ALNYLAM PHARMA INC
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