Liver transfection technology has made significant advances over the past few years, especially in the realm of gene therapy. The ultimate goal is to develop safe and effective methods for delivering therapeutic genes to the liver. Here are some of the key advancements in the field:

1. Use of AAV Serotypes: Significant progress has been made in identifying and utilizing AAV serotypes that can specifically target and transfect liver cells. AAV8 and AAV9, for instance, are known for their high transduction efficiency in hepatocytes.
2. Capsid Engineering and Directed Evolution of AAV: Researchers are using techniques like directed evolution to generate novel AAV capsids with improved liver tropism, transduction efficiency, and evasion of pre-existing immunity.
3. Non-Viral Vector Improvements: Improvements in nanoparticle design and other non-viral vectors have increased their efficiency and specificity. For example, lipid nanoparticles have been used successfully in mRNA vaccines (like the COVID-19 vaccines from Pfizer-BioNTech and Moderna) and show promise for gene delivery.
4. Gene Editing Technologies: The advent of gene editing technologies like CRISPR-Cas9 has revolutionized the field of gene therapy. CRISPR allows for precise editing of genes and has the potential to permanently cure genetic liver diseases by correcting the underlying genetic defect.
5. Hydrodynamic Gene Delivery: Although primarily used in small animals due to its invasiveness, modifications of the hydrodynamic delivery method are being researched to make it more applicable in larger animals and potentially in humans.
6. Liver-Specific Promoters and miRNA Targets: The use of liver-specific promoters in the gene construct ensures that the delivered gene is primarily expressed in the liver. Similarly, incorporating miRNA targets into the construct that are bound and activated by miRNAs present in off-target tissues can lead to the degradation of the construct in those tissues, thereby improving liver specificity.
7. Immunomodulation Strategies: New strategies are being developed to modulate the immune response to gene therapy, such as the use of immunosuppressive drugs or the development of strategies to avoid pre-existing immunity.
8. Liver Organoids and In Vitro Models: The development of liver organoids (3D cell culture systems that replicate aspects of liver structure and function) allows for more effective in vitro testing of gene delivery strategies.

These advancements are rapidly progressing, with numerous ongoing pre-clinical and clinical trials investigating new liver transfection methods and their application in treating a variety of liver diseases. However, challenges remain, such as improving specificity, reducing immunogenicity, and ensuring long-term safety and effectiveness of these gene therapy techniques. As of my knowledge cut-off in September 2021, these are areas of active research.