Provided herein are methods and compositions for increasing fetal hemoglobin levels in a cell by disrupting BCL11A expression at the genomic level. Also provided herein are methods and compositions relating to the treatment of hemoglobinopathies by reinduction of fetal hemoglobin levels.

Provided herein are methods and compositions for increasing fetal hemoglobin levels in a cell by disrupting BCL11A expression at the genomic level. Also provided herein are methods and compositions relating to the treatment of hemoglobinopathies by reinduction of fetal hemoglobin levels.

The invention relates to methods of cardiovascular imaging and/or measurement of blood markers for detecting, diagnosing and/or prognosing cardiac or myocardial microbleeds, especially in subject with hypertension and cardiovascular diseases. Treatment methods are also provided for subjects identified, diagnosed, prognosed, or detected with cardiac or myocardial microbleeds. In some embodiments, the subject has hypertension-induced microbleeds, but has not had a myocardial infarction or reperfusion therapy.

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.

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.

Provided herein is a method for treating an inflammatory bowel disease in a subject in need thereof, the method comprising administering a therapeutically effective amount of a hemoglobin to the subject.

Provided herein are compositions and methods of using base editors comprising a polynucleotide programmable nucleotide binding domain and a nucleobase editing domain in conjunction with a guide polynucleotide. Also provided herein are base editor systems for editing nucleobases of target nucleotide sequences.

Certain aspects of the present invention relate to modified hemoglobin proteins comprising at least one modification (e.g., at the thiol group of an exogenous amino acid residue) for homogenous conjugation of one or more polymeric moieties e.g. polyethylene glycol or derivatives thereof. Also included herein are methods of using such modified proteins and compositions comprising such proteins, e.g. in therapy.

Certain aspects of the present invention relate to modified hemoglobin proteins comprising at least one modification (e.g., at the thiol group of an exogenous amino acid residue) for homogenous conjugation of one or more polymeric moieties e.g. polyethylene glycol or derivatives thereof. Also included herein are methods of using such modified proteins and compositions comprising such proteins, e.g. in therapy.

The present invention is drawn to artificial metalloenzymes for use in cyclopropanation reactions, amination and C—H insertion.