Complement Factor H Gene Knockout Rat as a Model of C3 Glomerulopathy
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsKishor Devalaraja-Narashimha, Jeffrey D. Lee, Lori Morton
Life of this patent
Estimating the term…
Abstract
Rat cells and rats comprising an inactivated Cfh locus and methods of making and using such rat cells and rats are provided. The rats comprising an inactivated Cfh locus model C3 glomerulopathy (C3G). Methods are provided for using such rats comprising an inactivated Cfh locus to assess in vivo efficacy of putative C3G therapeutic agents.
Claims70
A genetically modified rat comprising an inactivated endogenous Cfh locus.
The genetically modified rat of any preceding claim, wherein the rat is a male.
The genetically modified rat of any preceding claim, wherein the rat is homozygous for the inactivated endogenous Cfh locus.
The genetically modified rat of any preceding claim, wherein the rat has one or more symptoms of C3 glomerulopathy (C3G).
The genetically modified rat of any preceding claim, wherein the genetically modified rat has decreased circulatory C3 levels compared to a wild type rat.
The genetically modified rat of any preceding claim, wherein the genetically modified rat has increased blood urea nitrogen levels, increased serum cystatin C levels, or increased urinary albumin levels compared to a wild type rat.
The genetically modified rat of any preceding claim, wherein the genetically modified rat has increased C3 deposition in the kidneys compared to a wild type rat.
The genetically modified rat of any preceding claim, wherein the genetically modified rat has increased C5b-9 deposition in the kidneys compared to a wild type rat.
The genetically modified rat of any preceding claim, wherein the genetically modified rat has increased glomerular pathology compared to a wild type rat.
The genetically modified rat of any preceding claim, wherein the genetically modified rat has a decreased lifespan compared to a wild type rat.
A genetically modified rat cell comprising an inactivated endogenous Cfh locus.
A genetically modified rat genome comprising an inactivated endogenous Cfh locus.
A rat Cfh gene comprising a targeted genetic modification that inactivates the rat Cfh gene.
A nuclease agent for use in inactivating a rat Cfh gene, wherein the nuclease agent targets and cleaves a nuclease target site in the Cfh gene.
A method of making a genetically modified rat cell comprising an inactivated endogenous Cfh locus, comprising introducing into a rat cell a nuclease agent that targets a target sequence proximate to the start codon of the endogenous Cfh genomic locus, wherein the nuclease agent cleaves the target sequence to produce the genetically modified rat cell comprising the inactivated endogenous Cfh locus.
A method of making a genetically modified rat genome comprising an inactivated endogenous Cfh locus, comprising contacting a rat genome with a nuclease agent that targets a target sequence proximate to the start codon of the endogenous Cfh genomic locus, wherein the nuclease agent cleaves the target sequence to produce the genetically modified rat genome comprising the inactivated endogenous Cfh locus.
A method of making an inactivated rat Cfh gene, comprising contacting a rat Cfh gene with a nuclease agent that targets a target sequence proximate to the start codon of the endogenous Cfh genomic locus, wherein the nuclease agent cleaves the target sequence to produce the inactivated rat Cfh gene.
Dependencies are inferred from the claim text.