RIGERR (Resources for Investigating Genetic and Epigenetic Regulation of Renal Disease)

The RIGERR program is funded by an RC2 grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The goal of RIGERR is to generate innovative resources and tools of high research community-wide value for elucidating the mechanism by which human DNA sequence variants contribute to kidney disease.

Find us on Twitter @MCW_RIGERR

Kidney disease involves rare and common DNA sequence variations. A definitive approach to identifying functional sequence variants and their effector genes and studying the mechanism involved is to specifically edit the variants and examine the effect of the editing on gene expression, cellular function, and molecular mechanisms.

Performing genetic engineering in human induced pluripotent stem cells (iPSCs), followed by iPSC differentiation to cells relevant to disease of interest, represents an excellent combination of a technically amenable system and physiologically relevant cellular context for such studies.

RIGERR generates human iPSC lines that have been precisely edited for DNA sequence variants relevant to kidney disease. The reference and alternative or normal and mutant alleles of a variant or variants of interest are reconstituted in well-controlled, isogenic human iPSC lines. The edited iPSC lines are available to the research community for studies of genetic and epigenetic mechanisms of kidney disease.

Investigators are invited to nominate DNA sequence variants for editing by RIGERR. Please complete and submit the target nomination form.

Download the form below to nominate a DNA sequence variant(s) for editing

RIGERR Target Nomination Form

More details to come

Examples of studies using genome-edited iPSCs:

Gupta RM, Hadaya J, Trehan A, Zekavat SM, Roselli C, Klarin D, Emdin CA, Hilvering CRE, Bianchi V, Mueller C, Khera AV, Ryan RJH, Engreitz JM, Issner R, Shoresh N, Epstein CB, de Laat W, Brown JD, Schnabel RB, Bernstein BE, Kathiresan S. A genetic variant associated with five vascular diseases is a distal regulator of endothelin-1 gene expression. Cell. 2017;170:522-533.e515 https://pubmed.ncbi.nlm.nih.gov/28753427/

Lo Sardo V, Chubukov P, Ferguson W, Kumar A, Teng EL, Duran M, Zhang L, Cost G, Engler AJ, Urnov F, Topol EJ, Torkamani A, Baldwin KK. Unveiling the role of the most impactful cardiovascular risk locus through haplotype editing. Cell. 2018;175:1796-1810.e1720 https://pubmed.ncbi.nlm.nih.gov/30528432/

Dorison A, Ghobrial I, Graham A, Peiris T, Forbes T, See M, Das M, Saleem M, Quinlan C, Lawlor K, Ramialison M, Howden S, Little M. Kidney Organoids Generated Using an Allelic Series of NPHS2 Point Variants Reveal Distinct Intracellular Podocin Mistrafficking. J Am Soc Nephrol. 2022 Sep 27:ASN.2022060707 https://pubmed.ncbi.nlm.nih.gov/36167728/