• The DMPK gene is mainly expressed in skeletal muscle, heart, brain and several other tissues. In these tissues, DMPK is involved in the normal function and regulation of muscles. Myotonic dystrophy type 1 (DM1) is caused by the expansion of CTG nucleotide repeats in the DMPK gene. Normally, the number of CTG repeats ranges from 5 to 37 times, but in patients with DM1, this repeat can increase to several hundreds or even thousands of times.
• TFR1 plays a crucial role in regulating the distribution of iron in the brain, involving multiple biological processes such as cell metabolism, development, myelination, and neurotransmission. Due to the expression of TfR1 in brain endothelial cells, it serves as an ideal target for drug delivery. Various drug delivery strategies targeting TfR1 have been developed to effectively penetrate the blood-brain barrier and promote therapeutic interventions for brain diseases.
• Gene editing strategy: The exons 1~15 of mouse Dmpk gene that encode the full-length protein were replaced by human DMPK exons 1~15 in B-hTFR1/hDMPK mice. The promoter, 5’UTR and 3’UTR region of the mouse gene were replaced by human counterparts. The exons 4-19 of mouse Tfr1 gene that encode the extracellular region were replaced by human TFR1 exons 4-19 in B-hTFR1/hDMPK mice.
• In vivo efficacy: Human DMPK targeted Antibody oligonucleotide conjugates drug (AOC) was efficacious in B-hTFR1/hDMPK mice.
• Application: This product is used for pharmacodynamics and safety evaluation of Myotonic dystrophy type 1 (DM1).

• The exons 1~15 of mouse Dmpk gene that encode the full-length protein were replaced by human DMPK exons 1~15 in B-hTFR1/hDMPK mice. The promoter, 5’UTR and 3’UTR region of the mouse gene were replaced by human counterparts. 
• The exons 4-19 of mouse Tfr1 gene that encode the extracellular region were replaced by human TFR1 exons 4-19 in B-hTFR1/hDMPK mice.

The inhibitory efficiency of the AOC drug against human DMPK in heterozygous B-hTFR1/hDMPK mice. The AOC drug (AOC1001 analog, in-house), naked antibody (AOC1001-Ab, in-house) and PBS were administered to the heterozygous B-hTFR1/hDMPK mice individually on day 0. The mice were sacrificed on day 7, and the heart, liver, gastrocnemius muscle and tibialis anterior muscle were collected to detect the expression level of human DMPK mRNA by qPCR. The human DMPK mRNA in the treatment groups (AOC) were significantly reduced compared to the control groups (naked antibody and PBS), demonstrating that B-hTFR1/hDMPK mice provide a powerful preclinical model for in vivo evaluation of human DMPK targeted AOC drug. Values are expressed as mean ± SEM.