The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding a Serine Protease Inhibitor Kazal-type (SPINK) polypeptide (e.g., a SPINK5 polypeptide); viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for the treatment of Netherton Syndrome); and articles of manufacture or kits thereof.