Provided herein are Complement Factor I (CFI) variants that exhibit at least one improved characteristic relative to a wild type CFI. CFI variants of the disclosure can exhibit tunable specificity and activity. Also included are CFI-containing fusion constructs comprising at least one domain of CFI, for example, wild type full length CFI fused to human serum albumin. Also included are methods of making and using such CFI variants and fusion constructs. The CFI variants and fusion constructs provided herein may be useful for treating a disease or condition associated with dysregulation of the complement system or a deficiency of CFI.

Aspects of the present invention relate to the recombinant production of a mature complement system protein. Certain embodiments of the present invention relate to recombinant production of fully mature human complement Factor I protein (CFI). Included herein are details of an expression vector with which to recombinantly express fully mature human CFI from mammalian cells. Further disclosed are chromatography steps with which to purify recombinantly expressed CFI. Certain aspects of the present invention relate to the use of an expression system in gene therapy and the like. Certain embodiments of the present invention relate to use of said vector as a medicament, for example for use in the treatment of complement-mediated disorders.

The present disclosure provides compositions and methods for treating, preventing, or inhibiting diseases of the eye. In one aspect, the disclosure provides recombinant CF1 adeno-associated virus (rAAV) vectors comprising a complement system gene.

A product comprising (i) a Complement Factor I (CFI) cofactor; and (ii) Complement Factor I (CFI), or nucleotide sequences encoding therefor, as a combined preparation for simultaneous, separate or sequential use in therapy.

Polypeptides comprising a C3b binding region and a C3d inactivating region are disclosed, as well as nucleic acids and vectors encoding proteolytic such polypeptides. Also disclosed are cells and compositions comprising such polypeptides, and uses and methods using the same.

The disclosure provides, in part, compositions comprising mature recombinant mature Complement Factor I (CFI) protein and methods of making and using those compositions.

Polypeptides comprising a C3b binding region and a C3d inactivating region are disclosed, as well as nucleic acids and vectors encoding such polypeptides. Also disclosed are cells and compositions comprising such polypeptides, and uses and methods using the same.

Provided herein are pharmaceutically acceptable formulations comprising wild type Complement Factor I (CFI) and variants thereof; in some embodiments the wild type CFI and variants thereof are part of a fusion construct, e.g. a fusion construct comprising human serum albumin. The formulations stabilize CFI against acute stresses during storage in either a liquid or lyophilized state. Also provided are methods of making the formulations, and methods of using the formulations in the treatment of diseases.