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US 12,214,055 B2Granted
Systems and methods for treating hyper-igm syndrome
OwnerCecillia Cotta-Ramusino, Carrie M. Margulies +2inventors
InventorsCecillia Cotta-Ramusino, Carrie M. Margulies, Luigi Naldini, Pietro Genovese
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Abstract
Disclosed herein are genome editing systems and related methods which allow for treatment of Hyper IgM Syndrome, a group of disorders characterized by defective CD40 signaling. The compositions and methods described herein rely on the use of donor templates comprising a CD40L exons to restore proper CD40 signaling and B cell class switch recombination.
Claims20
An isolated oligonucleotide donor template which comprises, from 5′ to 3′, A1-N-UTR-pA-A2, wherein
- A1 is a homology arm that is substantially identical to a first homology arm of a target CD40L nucleic acid;
- N is a cargo comprising one or more of exons 2-5 of a CD40L gene;
- UTR is a CD40L 3′ untranslated region (UTR);
- pA is a polyA tail;
- and
- A2 is a homology arm that is substantially identical to a second homology arm of the target CD40L nucleic acid,
- and wherein the cargo does not comprise exon 1 of CD40L.
4 more elements
A method of altering a cell, comprising the steps of:
- forming, in a target CD40L nucleic acid of the cell, at least one single- or double-strand break at a cleavage site, wherein the target CD40L nucleic acid comprises:
- a first homology arm 5′ to the cleavage site and a second homology arm 3′ to the cleavage site, and
- recombining an exogenous oligonucleotide donor template with the target CD40L nucleic acid by homologous recombination to produce an altered CD40L nucleic acid, wherein the exogenous oligonucleotide donor template comprises a first donor homology arm that is substantially identical to the first homology arm, a cargo comprising one or more of exons 2-5 of a CD40L gene, a 3′ CD40L untranslated region (UTR), a polyA tail, and a second donor homology arm that is substantially identical to the second homology arm, and wherein the cargo does not comprise exon 1 of CD40L, thereby altering the cell.
Dependencies are inferred from the claim text.