Patent ID: 8053232

Claim:
An isolated liver cell comprising a nucleic acid molecule wherein said nucleic acid molecule comprises: a) one or more target binding domains that target binding of the nucleic acid molecule to a defective exon of a SERPINA1 pre-mRNA expressed from an endogenous defective SERPINA1 sequence within the cell; b) a 3′ splice region comprising a branch point and a 3′ splice acceptor site; c) a spacer region that separates the 3′ splice region from the target binding domain; d) a nucleotide sequence to be trans-spliced to the target pre-mRNA wherein said nucleotide sequence encodes a corrective SERPINA1 exon which forms a chimeric nucleic acid molecule with endogenous SERPINA1 pre-mRNA, wherein upon trans-splicing, a corrected mRNA is formed; and e) a Tia-1 binding sequence within 100 nucleotides of a 5′ donor site, wherein said nucleic acid molecule is recognized by nuclear splicing components within the cell, and wherein a defective exon of the endogenous SERPINA1 pre-mRNA is replaced.