The present invention is directed to a design of and a method to synthesize polycations for gene (DNA and RNA) delivery. According to this design, the polycations (also said cationic polymers) are formed by polymerization of endogenous monomers bearing sufficient amino groups through degradable bonds with linker molecules. The amino group-bearing monomers are those naturally existing or nontoxic to human body. The linker molecules are those which are not only degradable to nontoxic fragments but also able to release the amino group-bearing monomers in their native state upon degradation. Some examples for the endogenous amino group-bearing monomers are spermine and spermidine (or their derivatives). Examples for the degradable chemical bonds formed between the amino group-bearing monomers are imines. In order to improve degradability or proton sponging effect, low pKa (<8) amino group(s), free amino groups generated by polymer degradation (such as those generated by degradation of imine linkages), or other electron donating group(s) such as imidazole, pyrazole, pyridine, pyrimidine, or even benzene is incorporated in the linker between the two (or three) reactive groups for linking the amino group-bearing monomers. These polycationic carrier systems can be used for nano-encapsulation and transfection of gene materials.
