This disclosure provides for methods and compositions for the expression and secretion of heme-containing polypeptides.

The present invention relates to methods and pharmaceutical compositions for the treatment of Erythropoietic Protoporphyria. In particular, the present invention relates to a method for increasing the amount of functional FECH in a erythroid cell carrying the hypomorphic allele IVS3 48C/T (rs2272783) in trans to a deleterious mutation in the FECH gene comprising the step of consisting of bringing the erythroid cell into contact with at least one antisense oligonucleotide (ASO) comprising the sequence as set forth by SEQ ID NO: 2 (5 gcagcctgagaaatgtttt 3) to prevent splicing of the cryptic exon inserted into the mutant IVS3 48C/T (rs2272783) FECH mRNA.

The present invention relates to methods and pharmaceutical compositions for the treatment of Erythropoietic Protoporphyria. In particular, the present invention relates to a method for increasing the amount of functional FECH in a erythroid cell carrying the hypomorphic allele IVS3 48C/T (rs2272783) in trans to a deleterious mutation in the FECH gene comprising the step of consisting of bringing the erythroid cell into contact with at least one antisense oligonucleotide (ASO) comprising the sequence as set forth by SEQ ID NO: 2 (5 gcagcctgagaaatgtttt 3) to prevent splicing of the cryptic exon inserted into the mutant IVS3 48C/T (rs2272783) FECH mRNA.

A method to make Co- or Ni-substituted protoporphyrin IX by incubating an E. coli strain in a rich medium containing iron ions and added Co.sup.2+ or Ni.sup.2+ ions, for a time and under conditions wherein the E. coli strain produces Co- or Ni-substituted protoporphyrin IX. The E. coli host may be transformed to contain and express a gene construct encoding a mutant EcHemH including a L13R mutation.

Plants and plant tissue such as leaves comprising leghemoglobin are produced by modifying the genome of the plant or introducing leghemoglobin coding or regulatory sequences into the plant. Plants, leaves, fruits, tubers, roots, seeds, and protein compositions comprising leghemoglobin are provided. Protein compositions comprising leghemoglobin, such as isolates and concentrates, can be made from the plants, tissue, fruits, tubers, roots, seeds and leaves. Additionally, methods for generating and using plants, tissue, fruits, tubers, roots, seeds, leaves and protein compositions comprising leghemoglobin are disclosed.