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1. WO2020006630 - LIGHT-INDUCIBLE PROTEIN AGGREGATION SYSTEM FOR MODELING PROTEINOPATHIES AND NEURODEGENERATIVE DISORDERS

Publication Number WO/2020/006630
Publication Date 09.01.2020
International Application No. PCT/CA2019/050914
International Filing Date 03.07.2019
IPC
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N
MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICRO-ORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15
Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
09
Recombinant DNA-technology
63
Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38
Medicinal preparations containing peptides
16
Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
45
Medicinal preparations containing active ingredients not provided for in groups A61K31/-A61K41/132
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
K
PEPTIDES
1
General processes for the preparation of peptides
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
K
PEPTIDES
14
Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
415
from plants
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N
MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICRO-ORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15
Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
09
Recombinant DNA-technology
11
DNA or RNA fragments; Modified forms thereof
29
Genes encoding plant proteins, e.g. thaumatin
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N
MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICRO-ORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15
Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
09
Recombinant DNA-technology
63
Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
79
Vectors or expression systems specially adapted for eukaryotic hosts
85
for animal cells
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N
MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICRO-ORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
5
Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
10
Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
P
FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
21
Preparation of peptides or proteins
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
Q
MEASURING OR TESTING PROCESSES INVOLVING ENZYMES OR MICRO-ORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
1
Measuring or testing processes involving enzymes or micro-organisms; Compositions therefor; Processes of preparing such compositions
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
Q
MEASURING OR TESTING PROCESSES INVOLVING ENZYMES OR MICRO-ORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
1
Measuring or testing processes involving enzymes or micro-organisms; Compositions therefor; Processes of preparing such compositions
02
involving viable micro-organisms
04
Determining presence or kind of micro-organism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
12
Nitrate to nitrite reducing bacteria
[IPC code unknown for C12Q 1/6897]
G PHYSICS
01
MEASURING; TESTING
N
INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33
Investigating or analysing materials by specific methods not covered by groups G01N1/-G01N31/131
48
Biological material, e.g. blood, urine; Haemocytometers
C12N 15/63 (2006.01)
A61K 38/16 (2006.01)
A61K 45/00 (2006.01)
C07K 1/00 (2006.01)
C07K 14/415 (2006.01)
C12N 15/29 (2006.01)
CPC
A61K 38/16
A61K 45/00
C07K 1/00
C12N 15/63
C12N 15/85
C12N 5/10
Applicants
  • UNIVERSITÉ LAVAL [CA/CA]; 2325, rue de l'Université Québec, Québec G1V 0A6, CA
Inventors
  • OUESLATI, Abid; CA
Agents
  • ROBIC LLP; 630 Rene-Levesque Boulevard West, 20th Floor Montréal, Québec H3B 1S6, CA
Priority Data
62/693,66603.07.2018US
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) LIGHT-INDUCIBLE PROTEIN AGGREGATION SYSTEM FOR MODELING PROTEINOPATHIES AND NEURODEGENERATIVE DISORDERS
(FR) SYSTÈME D'AGRÉGATION DE PROTÉINES PHOTO-INDUCTIBLE POUR MODÉLISER DES PROTÉINOPATHIES ET DES TROUBLES NEURODÉGÉNÉRATIFS
Abstract
(EN)
A light-inducible intracellular protein aggregation system is described herein, which provides invaluable tools to study the role of protein aggregates in proteinopathies and to screen for novel therapeutic compounds. The system generally comprises a cell expressing an alpha-synuclein polypeptide or another proteopathic polypeptide that self-aggregates under pathogenic conditions, operably linked to a photoactivatable polypeptide. Illumination of the photoactivatable polypeptide with light having a wavelength sufficient for photoactivation triggers irreversible accumulation of intracellular protein aggregates comprising the alpha-synuclein polypeptide or proteopathic polypeptide. The intracellular protein aggregates can be made to accumulate in real-time during the illumination, thereby enabling spatiotemporal control of protein aggregation. In some embodiments, the intracellular protein aggregates may exhibit pathologically-relevant properties of those found in disease-associated proteinopathies, such as irreversibility, auto-perpetuation (seeding) activity, and comprising misfolded proteins rich in beta-sheet conformation.
(FR)
L'invention concerne un système d'agrégation de protéines intracellulaires photo-inductible qui fournit des outils précieux pour étudier le rôle d'agrégats de protéines dans des protéinopathies et pour cribler de nouveaux composés thérapeutiques. Le système comprend généralement une cellule exprimant un polypeptide d'alpha-synucléine ou un autre polypeptide protéopathique qui s'autoagrège dans des conditions pathogènes, liée de manière fonctionnelle à un polypeptide photoactivable. L'éclairage du polypeptide photoactivable avec de la lumière présentant une longueur d'onde suffisante pour la photoactivation déclenche l'accumulation irréversible d'agrégats de protéines intracellulaires comprenant le polypeptide d'alpha-synucléine ou le polypeptide protéopathique. Les agrégats de protéines intracellulaires peuvent être amenés à s'accumuler en temps réel pendant l'éclairage, ce qui permet une régulation spatio-temporelle de l'agrégation de protéines. Dans certains modes de réalisation, les agrégats de protéines intracellulaires peuvent présenter des propriétés pathologiquement pertinentes des agrégats présents dans des protéinopathies associées à des maladies, telles que l'irréversibilité, l'activité d'auto-perpétuation (ensemencement), et comprenant des protéines mal repliées riches en conformation de feuillets bêta.
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