The present disclosure provides expression constructs designed to provide for stable and/or inducible, tightly controlled production of genetically encoded payloads from engineered cells. These cassettes allow cells to be engineered to express genetically encoded payloads despite epigenetic silencing. As such, provided herein are expression systems for use in methods to engineer cells using CRISPR dCas9-activator systems such that expression of genetically encoded payloads (e.g., therapeutic proteins) can be optimized to overcome epigenetic silencing. In addition, provided herein are engineered cells comprising the expression systems.

A method of treating a synucleinopathy with a peptide (C)DQPVLPD (SEQ ID NO: 59), (C)DMPVLPD (SEQ ID NO: 60), (C)DSPVLPD (SEQ ID NO: 61), (C)DQPVLPDN (SEQ ID NO: 64), (C)DMPVLPDN (SEQ ID NO: 65), (C)DSPVLPDN (SEQ ID NO: 66), (C)HDRPVTPD (SEQ ID NO: 70), (C)DRPVTPD (SEQ ID NO: 71), (C)DVPVLPD (SEQ ID NO: 72), (C)DTPVYPD (SEQ ID NO: 73), (C)DTPVIPD (SEQ ID NO: 74), (C)HDRPVTPDN (SEQ ID NO: 75), (C)DRPVTPDN (SEQ ID NO: 76), (C)DVPVLPDN (SEQ ID NO: 78), (C)DTPVYPDN (SEQ ID NO: 79), (C)DQPVLPDG (SEQ ID NO: 81), (C)DMPVLPDG (SEQ ID NO: 82), (C)DSPVLPDG (SEQ ID NO: 83), (C)DHPVHPDS (SEQ ID NO: 86), (C)DMPVSPDR (SEQ ID NO: 87), (C)DRPVYPDI (SEQ ID NO: 90), (C)DHPVTPDR (SEQ ID NO: 91), (C)DTPVLPDS (SEQ ID NO: 93), (C)DMPVTPDT (SEQ ID NO: 94), (C)DAPVTPDT (SEQ ID NO: 95), (C)DSPVVPDN (SEQ ID NO: 96), (C)DLPVTPDR (SEQ ID NO: 97), (C)DSPVHPDT (SEQ ID NO: 98), (C)DAPVRPDS (SEQ ID NO: 99), (C)DMPVWPDG (SEQ ID NO: 100), (C)DRPVQPDR (SEQ ID NO: 102), (C)YDRPVQPDR (SEQ ID NO: 103), (C)DMPVDADN (SEQ ID NO: 105), DQPVLPD(C) (SEQ ID NO: 106), and DMPVLPD(C) (SEQ ID NO: 107.

A recombinant lentiviral vector includes a gene encoding a hepatocyte growth factor (HGF) protein. And a cell that is transfected with the lentivirus produced by using the vector is provided. The recombinant lentivirus includes a gene encoding a HGF protein, and a host cell transfected with the lentivirus maintains a high cell proliferation rate. Thus, a mesenchymal stem cell expressing HGF by being transfected with the lentivirus may be usefully employed as a cell therapeutic agent.

A recombinant lentiviral vector includes a gene encoding a hepatocyte growth factor (HGF) protein. And a cell that is transfected with the lentivirus produced by using the vector is provided. The recombinant lentivirus includes a gene encoding a HGF protein, and a host cell transfected with the lentivirus maintains a high cell proliferation rate. Thus, a mesenchymal stem cell expressing HGF by being transfected with the lentivirus may be usefully employed as a cell therapeutic agent.

Provided herein are compositions that include one or more adeno-associated virus (AAVs) vectors and methods of inducing differentiation of a hair cell using these vector(s).

Provided herein are compositions that include a single nucleic acid vector or two different nucleic acid vectors, and the use of these compositions to treat hearing loss in a subject.

Provided herein are compositions that include a single nucleic acid vector or two different nucleic acid vectors, and the use of these compositions to treat hearing loss in a subject.

Provided methods of using FLT3L-Fc fusion proteins, including doses and dosing regimens and schedules for administering FLT3L-Fc fusion proteins to a subject in need thereof.

Multispecific antagonists for targeting angiogenesis pathways are disclosed. The multispecific antagonists may be used for the treatment of disorders associated with angiogenesis pathways.

The invention provides compositions, methods, and kits for increasing transport of GDNF across the blood brain barrier while allowing its activity to remain substantially intact. The GDNF is transported across the blood brain barrier via one or more endogenous receptor-mediated transport systems.