CRISPR, mRNA, and Beyond: Nucleic Acid Therapeutics in Allergy and Immunology

The management of allergic and immunologic diseases has long centered on symptom management rather than disease modification. Conventional pharmacotherapy controls manifestations of the immune dysregulation but does little to treat the underlying cause. Newer monoclonal and small molecule therapies target downstream effectors of the type 2 inflammatory cascade, and allergen immunotherapy, while disease-modifying, requires years of administration for effect. Nucleic acid therapies represent a different approach that intervenes at the level of genetic information itself, at the DNA, RNA, or protein-production step. This includes mRNA treatments that direct cells to produce therapeutic proteins or modify allergen-specific immune responses; antisense oligonucleotides and small interfering RNAs that selectively silence disease genes; adeno-associated viral vectors for sustained gene delivery; and CRISPR-based systems that permanently edit the genome. Several technologies have advanced to clinical proof of concept including a CRISPR gene-editing therapy (lonvoguran ziclumeran) that reduced hereditary angioedema attacks by 87% compared with placebo in a randomized controlled trial. An inhaled DNAzyme targeting the intracellular transcription factor GATA3 attenuated allergen-induced late asthmatic responses by 34% in humans, and CD19 CAR-T cell therapy induced drug-free remission in severe autoimmune disease. As of 2025, 24 oligonucleotide therapeutics have received FDA approval, including donidalorsen, the first RNA-targeted prophylactic therapy approved for hereditary angioedema. This review examines each therapeutic technology, its mechanism and delivery strategy, and the evidence relevant to allergic and immunologic disease. Persistent challenges, including delivery beyond the liver, immune responses to viral vectors, and the need for long-term safety data, are addressed alongside a proposed integration with existing treatment paradigms.

Abstract from PubMed (PMID 43009097). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.