Physicochemical and biological evaluation of JR-131 as a biosimilar to a long-acting erythropoiesis-stimulating agent darbepoetin alfa.

Renal anemia is predominantly caused by a relative deficiency in erythropoietin (EPO). Conventional treatment for renal anemia includes the use of recombinant human EPO (rhEPO) or a long-acting erythropoiesis-activating agent named darbepoetin alfa, which is a modified rhEPO with a carbohydrate chain structure that differs from native hEPO. We have developed a biosimilar to darbepoetin alfa designated JR-131.

Enhanced internalization and endosomal escape of dual-functionalized poly(ethyleneimine)s polyplex with diphtheria toxin T and R domains.

A new multifunctional gene delivery system was constructed with diphtheria toxin's functional domains. Used functional domains are T domain for endosomal escape and R domain for efficient internalization into cell. In order to conjugate these domains into PEI polyplex, diphtheria toxin T and R domains-streptavidin fusion protein (DTRS) was prepared.

The conjugation of diphtheria toxin T domain to poly(ethylenimine) based vectors for enhanced endosomal escape during gene transfection.

The endosomal escape is a well-known serious obstacle for non-viral gene delivery. This is because of an acidic and enzymatic degradation of the contents of the endosome/lysosome. Therefore, the internalized gene needs to be efficient released into the cytosol to obtain the efficiently transfection efficiency.

Dual-ligand effect of transferrin and transforming growth factor alpha on polyethyleneimine-mediated gene delivery.

In order to enhance the internalization of exogenous gene and add cell specificity to non-viral vectors, receptor-binding elements have been widely utilized to mimic the virus infection. Herein, for the purpose of intensifying the effects of the ligand on gene delivery, dual receptor-binding elements, transferrin (Tf) and transforming growth factor alpha (TGFalpha), were introduced into the polyethyleneimine polyplex. The transfection and internalization efficiency by dual Tf- and TGFalpha-introduced polyplex (Tf&TGFalpha-polyplex) was examined in A549 and CHO-K1 cells, respectively.

In vitro gene delivery to HepG2 cells using galactosylated 6-amino-6-deoxychitosan as a DNA carrier.

A chitosan derivative, 6-amino-6-deoxy chitosan (6ACT), was galactosylated and was investigated as a gene carrier. A series of galactose-modified 6ACT (Gal-6ACT) with degrees of substitution (d.s.