Gene editing to improve joint function
Inventors
Millett, Peter J. • Russell, Iain Alasdair • Allen, Matthew J.
Assignees
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Publication Number
US-12290572-B2
Publication Date
2025-05-06
Expiration Date
Abstract
The present invention provides compositions and methods for treating joint disorders that are characterized by an inflammatory component. In some aspects, the compositions and methods are to prevent the progression of osteoarthritis and other arthritides and to treat osteoarthritis and other arthritides in a mammalian joint.
Core Innovation
A CRISPR gene-editing system is used in a pharmaceutical composition for the treatment or prevention of a joint disease or condition. The composition includes a nucleic acid encoding a Cas9 protein and at least one guide RNA targeting an IL-1α gene or an IL-1β gene, with the crRNA comprising a sequence complementary to a target sequence in exon 4 of the respective IL-1 gene.
The target sequence is adjacent to a protospacer adjacent motif (PAM) sequence for the Cas9 protein. The document describes gene-editing strategies directed to inflammatory joint disorders, including osteoarthritis, by editing synovial cells and chondrocytes. The editing is described as silencing or reducing inflammatory cytokine genes such as IL-1α and IL-1β.
Programmable nucleases are described, including CRISPR-Cas9, with other nuclease types referenced such as TALE and zinc-finger nucleases. Delivery concepts are described using viral vectors, including AAV, and local intra-articular injection, including controlled-release hydrogel and vehicle/formulation concepts. Experimental support in the document includes in vivo and in vitro assays for targeting IL-1α/IL-1β, and measurements of inflammatory biomarkers and gene-editing readouts.
Claims Coverage
Two independent claims are identified. Each claim requires a therapeutically effective CRISPR gene-editing system with Cas9 and a guide RNA directed to exon 4 of an IL-1 gene, where the guide RNA target is adjacent to a Cas9 PAM.
CRISPR gene-editing system targeting IL-1α exon 4 with Cas9 PAM adjacency
A pharmaceutical composition for the treatment or prevention of a joint disease or condition comprising a therapeutically effective amount of a CRISPR gene-editing system comprising a nucleic acid encoding a Cas9 protein and at least one guide RNA targeting an IL-1α gene, wherein the guide RNA comprises a crRNA complementary to a target sequence in exon 4 of the IL-1α gene and the target sequence is adjacent to a PAM sequence for the Cas9 protein.
CRISPR gene-editing system targeting IL-1β exon 4 with Cas9 PAM adjacency
A pharmaceutical composition for the treatment or prevention of a joint disease or condition comprising a therapeutically effective amount of a CRISPR gene-editing system comprising a nucleic acid encoding a Cas9 protein and at least one guide RNA targeting an IL-1β gene, wherein the guide RNA comprises a crRNA complementary to a target sequence in exon 4 of the IL-1β gene and the target sequence is adjacent to a PAM sequence for the Cas9 protein.
The claim coverage is focused on pharmaceutical compositions that include Cas9 plus guide RNA where the crRNA targets exon 4 of IL-1α or IL-1β and the target sequence is adjacent to a Cas9 PAM.
Stated Advantages
Documented Applications
No documented applications found
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