Liver delivery of long-acting expression solution

Liver delivery of long-acting expression solutions

Applicable to metabolic diseases caused by functional degeneration, genetic diseases caused by loss-of-function gene mutations, antibody therapy, etc. Extend the half-life of the protein itself by optimizing the structure of the target protein. mRNA can increase mRNA translation efficiency through codon optimization, UTR optimization and secondary structure optimization of sequences, so as to reduce the frequency and dose of medication and improve safety. Delivery vectors that deliver mRNA to target organs such as the liver can enhance expression efficiency while requiring low toxicity. Reducing the natural immune response induced by mRNA through chemical modifications can minimize immune reactions and thereby extend the half-life of mRNA itself. The mRNA therapy can meet the requirements of protein replacement therapy by optimizing these four aspects.

Protein long-lasting strategy

Scenarios where mRNA is unavailable

1.PEG modification technology

2.Fatty acid side chain modification

3.Glycosylation modification

4.Unnatural amino acid modifications

5.Microspheres

Exploration breakthrough: protein expression enhancement LNP solution

RhLNP-PE: Suitable for protein replacement or liver disease-related pipelines, Existing cooperation cases have achieved stable expression at low doses for over 25 days

Injection of 5ug firefly enzyme into the tail vein of mice MRNA-LNP, imaging after 24 hours

Inject 10ug mRNA-LNP into the tail vein of mice, collect blood at time points, and detect protein concentration Can achieve sustained expression of a certain protein A for up to 9 days, while the protein itself has a half-life of only 2 hours

Three cation library patents have been authorized, and one has been applied to the pipeline with no risk of FTO analysis

In addition, one cation library patent is currently under review, and one is being drafted.

Authorized cation library patent 1

Immune effect is better than commercial lipid A5

Authorized cation library patent 2

Fluorescent transfection efficiency within multiple liposomes is superior to commercial lipid MC3

Authorized cation library patent 3

Multiple intralipofluorescent transfection efficiencies Better than commercial lipid MC3 and Lipid M

Excellent safety

Authorized cation library patent 3

One formula patent has been submitted, and one is being drafted.

Excellent safety

SD rats were injected intravenously with 5mg/kg mRNA-LNP in the tail, and blood samples were collected at 120 hours to detect biochemical indicators, and no abnormalities were found.

Comparison of expression levels of different chemically modified mRNAs in cells

Transfected synovial cells SFL-secreted protein: Anti-FGF 18 polyclonal

Transfected chondrocytes CHON-secreted protein: Anti-FGF 18 polyclonal

Liver delivery of long-acting expression solution