23-01-2020 дата публикации
Номер: US20200024576A1
Принадлежит:
The present disclosure provides a 3-dimensional filamentous fiber matrix, systems comprising the matrix, and methods for using the matrix and the systems. 1. A three-dimensional filamentous fiber matrix comprising:a) a first cardiomyocyte population comprising a mutation in a gene encoding a gene product required for normal cardiomyocyte function, wherein the mutation reduces the level or the activity of the gene product; and/orb) a second cardiomyocyte population, wherein the second cardiomyocyte population is isogenic with the first cardiomyocyte population, but does not comprise the mutation.2. The matrix of claim 1 , wherein the gene product is selected from a cardiac myosin binding protein C polypeptide claim 1 , a cytoskeletal polypeptide claim 1 , δ-sarcoglycan (SGCD) claim 1 , β-sarcoglycan (SGCB) claim 1 , desmin (DES) claim 1 , lamin A/C (LMNA) claim 1 , vinculin (VCL) claim 1 , a sarcomeric/myofibrillar polypeptide claim 1 , α-cardiac actin (ACTC) claim 1 , troponin T (TNNT2) claim 1 , troponin I (TNNI3) claim 1 , β-myosin heavy chain (MYH7) claim 1 , myosin binding protein C (MBPC3) claim 1 , α-tropomyosin (TPM1) claim 1 , a Z-disk protein claim 1 , muscle LIM protein (MLP) claim 1 , cysteine and glycine-rich protein 3 (CSRP3) claim 1 , titin (TTN) claim 1 , telethonin/TCAP claim 1 , α-actinin-2 (ACTN2) claim 1 , nebulette (NEBL) claim 1 , myopalladin (MYPN) claim 1 , ANKRD1/CARP claim 1 , ZASP/LIM-domain binding 3 (LBD3) claim 1 , cardiac sodium channel gene SCN5A claim 1 , calcium homeostasis regulator phospholamban (PLN) claim 1 , desmoplakin (DSP) claim 1 , desmoglein-2 (DSG2) claim 1 , and desmocolin-2 (DSC2).3. The matrix of claim 1 , wherein the mutation is a loss-of-function mutation.4. The matrix of claim 1 , wherein the first and the second cardiomyocyte populations are human cardiomyocytes.5. The matrix of claim 1 , wherein the first cardiomyocyte population is genetically modified to produce a polypeptide calcium reporter.6. The matrix of ...
Подробнее