While viral vectors are efficient at delivering genes into cells, there are also non-viral methods that can be used for liver transfection. Non-viral methods generally have lower transfection efficiency, but they have the advantage of being less likely to induce immune responses and having larger cargo capacities.

Here are some non-viral methods used for liver transfection:

1. Liposome-based Transfection: Liposomes are lipid-based nanoparticles that can encapsulate DNA or RNA and facilitate their entry into cells. Cationic liposomes, which carry a positive charge, can complex with negatively charged nucleic acids and interact with the cell membrane to deliver their cargo into cells. There are commercially available liposomal transfection reagents specifically designed for in vivo use.
2. Hydrodynamic Injection: This technique involves the rapid injection of a large volume of DNA solution into the tail vein of an animal, usually a mouse. The high pressure forces the DNA into liver cells. However, this method can cause tissue damage and is not commonly used in humans.
3. Electroporation: In electroporation, an electric field is applied to cells to increase the permeability of the cell membrane, allowing DNA to enter. In vivo electroporation devices have been developed that can target specific organs, including the liver.
4. Ultrasound-guided Transfection: Ultrasound can be used to deliver DNA into cells, often with the help of microbubbles. The ultrasound waves cause the microbubbles to oscillate or burst, creating temporary pores in the cell membrane through which the DNA can enter.
5. Nanoparticle-based Delivery: Nanoparticles made of various materials, such as gold, silica, or polymers, can be used to deliver DNA into cells. The DNA can be either encapsulated inside the nanoparticles or attached to their surface. Some nanoparticles can be designed to specifically target liver cells, reducing off-target effects.
6. Naked DNA: Simply injecting naked DNA into the bloodstream can result in some level of liver transfection, as hepatocytes are naturally good at taking up DNA from the blood. However, this method generally has low efficiency.

As with viral methods, each non-viral method has its own advantages and disadvantages, and the best method will depend on the specific context and goals of the experiment or treatment.