Figure 1.

Gene Therapy

With the gene replacement strategy, a wild-type gene is expressed by a promoter within a viral vector to replace gene function in the setting of a loss-of-function variant. Gene silencing is typically used to reduce expression of a mutant gene (referred to as allele-specific silencing) and applies primarily to missense variants (ie, single-nucleotide substitutions) that alter protein function. For direct genome editing, using CRISPR-Cas9, a targeted DNA cleavage can be directed to a precise location in the genome determined by the unique sequence of a guide RNA (RNA). Figure created with biorender.com. AAV = adeno-associated virus; mRNA = messenger RNA.