NZ762841B2 - Gene therapy for retinitis pigmentosa - Google Patents

Gene therapy for retinitis pigmentosa Download PDF

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Publication number
NZ762841B2
NZ762841B2 NZ762841A NZ76284115A NZ762841B2 NZ 762841 B2 NZ762841 B2 NZ 762841B2 NZ 762841 A NZ762841 A NZ 762841A NZ 76284115 A NZ76284115 A NZ 76284115A NZ 762841 B2 NZ762841 B2 NZ 762841B2
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NZ
New Zealand
Prior art keywords
sequence
seq
mir
raav
promoter
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NZ762841A
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NZ762841A (en
Inventor
Matthew Adamowicz
Riordan Catherine O
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Genzyme Corporation
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Application filed by Genzyme Corporation filed Critical Genzyme Corporation
Priority claimed from NZ724622A external-priority patent/NZ724622A/en
Publication of NZ762841A publication Critical patent/NZ762841A/en
Publication of NZ762841B2 publication Critical patent/NZ762841B2/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
    • A61K48/0058—Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
    • A61K48/0066—Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • C—CHEMISTRY; METALLURGY
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering N.A.
    • C12N2310/141—MicroRNAs, miRNAs
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/34—Allele or polymorphism specific uses
    • C—CHEMISTRY; METALLURGY
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    • C12N2330/00—Production
    • C12N2330/50—Biochemical production, i.e. in a transformed host cell
    • C12N2330/51—Specially adapted vectors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14141—Use of virus, viral particle or viral elements as a vector
    • C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof

Abstract

method for treating retinitis pigmentosa in a mammal, comprising administering to the eye of the mammal a recombinant adeno-associated virus (rAAV) viral particle comprising a rAAV vector comprising nucleic acid encoding a miR-708.

Claims (30)

1. Use of a composition comprising a first rAAV viral particle and a second rAAV viral particle in the manufacture of a medicament for treating retinitis pigmentosa caused by d sin in a human, wherein the first rAAV viral particle comprises a first rAAV vector comprising nucleic acid encoding a miR-708, wherein the second rAAV viral particle comprises a second rAAV vector comprising nucleic acid encoding ype rhodopsin, and wherein expression of the wild-type rhodopsin is refractory to suppression by miR-708.
2. Use of a composition comprising a first rAAV viral le and a second rAAV viral particle in the cture of a medicament for treating endoplasmic reticulum (ER) stress caused by mutated sin in a human, wherein the first rAAV viral particle comprises a first rAAV vector comprising c acid encoding a miR-708, wherein the second rAAV viral particle comprises a second rAAV vector comprising nucleic acid encoding wild-type rhodopsin , and wherein expression of the wildtype rhodopsin is refractory to ssion by miR-708.
3. The use of claim 1 or claim 2, wherein the medicament reduces one or more cellular markers of ER stress.
4. The use of claim 3, wherein the one or more cellular marker of ER stress is spliced XBP-1, CHOP or Grp78.
5. The use of any one of claims 1-4, wherein the nucleic acid ng miR-708 is operably linked to a promoter.
6. The use of claim 5, wherein the promoter expresses the miR-708 in photoreceptor cells.
7. The use of claim 5, wherein the promoter comprises a rhodopsin kinase (RK) promoter or an opsin promoter.
8. The use of claim 5, wherein the promoter is the chicken ß-actin (CBA) promoter.
9. The use of claim 5, wherein a sequence from a minute virus of mouse (MVM) intron is located 3’ to the promoter.
10. The use of claim 9, wherein the MMV intron comprises the nucleotide sequence of SEQ ID NO:23. 20338996_1 ters) P42129NZ01
11. The use of claim 5, wherein the promoter further comprises: i. a CMV enhancer; ii. a sequence from a photoreceptor specific transcription factor; iii. a sequence from a rod photoreceptor specific transcription factor; iv. a sequence from a neural retinal basic zipper factor; v. a sequence from a cone rod homeobox-containing transcription factor sequence; vi. a neural retinal basic leucine zipper factor, a CMV enhancer and an Opsin promoter; vii. a neural retinal basic leucine zipper factor, a CMV enhancer, an Opsin promoter, and an MVM intron; viii. a neural l basic leucine zipper factor sequence comprising SEQ ID NO:30; ix. a sequence from a cone rod homeobox-containing transcription factor sequence comprising SEQ ID NO:28; x. a CMV er comprising SEQ ID NO:29 and at least one or more of a sequence from a photoreceptor specific ription factor, a sequence from a rod photoreceptor ic transcription factor, a sequence from a neural retinal basic zipper factor comprising SEQ ID NO:30; a sequence from a cone rod homeobox-containing transcription factor sequence comprising SEQ ID NO:28; xi. a neural retinal basic leucine zipper factor comprising SEQ ID NO:30, a CMV enhancer comprising SEQ ID NO:29 and an Opsin promoter comprising SEQ ID NO:22; or xii. a neural retinal basic leucine zipper factor comprising SEQ ID NO:30, a CMV enhancer comprising SEQ ID NO:29, an Opsin er sing SEQ ID NO:22, and an MVM intron comprising SEQ ID NO:23.
12. The use of claim 5, wherein the er further comprises a CMV enhancer and at least one or more of a sequence from a photoreceptor specific transcription factor, a sequence from a rod photoreceptor specific transcription , a sequence from a neural retinal basic zipper factor; a sequence from a cone rod homeobox-containing ription factor sequence.
13. The use of claim 5, wherein the promoter r comprises a CMV enhancer sing SEQ ID NO:29.
14. The use of any one of claims 1-13, wherein the nucleic acid encoding miR-708 is embedded in an intron.
15. The use of any one of claims 1-13, wherein the nucleic acid encoding miR-708 comprises an endogenous miR-708 scaffold or a miR-155 scaffold. 20338996_1 (GHMatters) P42129NZ01
16. The use of any one of claims 1-13, wherein the rhodopsin is human rhodopsin.
17. The use of any one of claims 1-16, wherein the nucleic acid encoding rhodopsin comprises a substitution, insertion or deletion of c acid in the miR-708 target sequence.
18. The use of claim 17, wherein the substitution, insertion or deletion reduces or prevents recognition by 8.
19. The use of any one of claims 1-18, wherein the rhodopsin lacks the 3’ untranslated region (UTR) miR-708 target sequence.
20. The use of any one of claims 1-19, wherein the nucleic acid encoding miR-708 comprises the nucleic acid of SEQ ID NO:1.
21. The use of any one of claims 1-20, wherein the sin comprises the amino acid sequence of SEQ ID NO:2.
22. The use of any one of claims 1-20, wherein the nucleic acid encoding the rhodopsin comprises nucleic acid of SEQ ID NO:3.
23. The use of any one of claims 1-22, wherein the rAAV viral particle comprises a recombinant viral genome comprising a cleotide of SEQ ID NO:5.
24. The use of any one of claims 1-23, wherein the rAAV viral particle comprises an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAVrh8, AAVrh8R, AAV9, AAV10, AAVrh10, AAV11, AAV12, AAV2R471A, AAV2/2-7m8, AAV DJ, AAV2 N587A, AAV2 E548A, AAV2 N708A, AAV V708K, a goat AAV, AAV1/AAV2 chimeric, bovine AAV, or mouse AAV capsid rAAV2/HBoV1 serotype capsid.
25. The use of claim 24, wherein the rAAV viral particle comprises an AAV serotype 5 capsid.
26. The use of any one of claims 1-25, n the rAAV particles are to be injected into the inal space of the retina of the human at one or more locations.
27. The use of any one of claims 1-25, wherein the rAAV particles are to be injected intravitreally to the human.
28. The use of any one of claims 1-26, wherein the retinitis pigmentosa is autosomal dominant tis tosa or autosomal recessive retinitis tosa. 20338996_1 (GHMatters) P42129NZ01
29. The use of any one of claims 1-28, wherein a first rAAV particle encoding the miR-708 and a second rAAV particle encoding rhodopsin are to be administered to the human at the same time or the first rAAV particle ng the miR-708 and the second rAAV particle encoding the rhodopsin are to be administered to the human sequentially.
30. The use of any one of claims 1-29, wherein the human has a P23H mutation in the nous rhodopsin gene
20338996. _1 (GHMatters) P42129NZ01 .mmvE mmmmmm mama“ a.» N g???axm a?w x\x\3555555555sxsxsxsxanassxs5555555555555\ aggg??m?mm? “R wa?w “w V V .AAAAAAAAAAAA\\‘h‘h\\\\\\\\\\\AAAAAAAAAAAAAAAAAAAAA\\\«\\\AAAAAAAAAAAAAAAA\\‘\\\\\\\\\\\‘\AAAAAAAAAAAAAAAA\\\.$\‘AAAAAAAAAAAAAAA\\\‘\\\\\\\\\\AAAAAAAAAAAAAAAAAAAA\\~WAAA\\\\\\\\\\\\\\\\\Amm«x A\\\\\\\\\\\\\\\\\\\\\\ .“‘x {M “\ \us xxux m»\ ‘x §$§ §§§ sax: $.me aM s; $3 ngm?ww‘ ?gxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxx\\\\\\\\\xxxxxxxxxx\\\\\\\\\xxxxxxxxxx\\\\\\\\\xxxxxxxx\\\\\\\\\\\xxxxxxxx\\\\\\\\\xx\\\\\\\\\\\\\\\\\\\\\\\ .0."— w
58306. 4 CBA Promoter Mg??? 3222323333 5 ?amingzgéa E32738 33 33 33 :3 33 33 33; 3:3; 33: 33- 33.; 3:3 3 3» 3:3 3:3 3:3 3:3 292322 33333333; 332333333333333 333333 Exgémzmm RNA WW 6 2.353% FIGmaizmm CHOP ?g Ki} §‘§‘~‘ $73 w {4% N S} \Z‘i €333 sit} £1? £§v§3§$$i§§£§§§§ 31mg m?? $33M § «x? .«\ \\v “5‘; “V ._ N\.t\;W N: 2.23%; *“ ‘R\) R3 RX? 7B ?badaa?n FIGmm“ aga?mmggt’; :3ng RM mi§€$§$ : W m m “3 ?g {\g {x \t‘e m FIGS(1&1? am edgy-glam 7A m": gym-w FIGawe §x)3 m e» k? n m «K one: a; iii$d§3§3£3i§§§ §3§€3§§ “mmsml mgK , .u.maximum §§ K“xNN“m V Willi? .mvE w: wm?w? 2% .m .w ..............Kama“ N“ mmm?m will!!!“ cgmwmaxw .0."— 33%ch (ma) uoassmdxa uxsdopoua “fa w mxmw?g .me mammmm?mm emg?owég?mn “33> .0."— mmwém? (- E£Mn comm aSN 33 can; (9|?le 01 SMIBWH) 30138011 as9311“” Plod
NZ762841A 2015-03-20 Gene therapy for retinitis pigmentosa NZ762841B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201461969027P 2014-03-21 2014-03-21
NZ724622A NZ724622A (en) 2014-03-21 2015-03-20 Gene therapy for retinitis pigmentosa

Publications (2)

Publication Number Publication Date
NZ762841A NZ762841A (en) 2023-11-24
NZ762841B2 true NZ762841B2 (en) 2024-02-27

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