Neurofibromin 1 pre-messenger RNA (NF1 pre-mRNA) (NF1 pre-mRNA)

Neurofibromin 1 (NF1) pre-messenger RNA is the primary transcript of the NF1 gene, which encodes neurofibromin, a critical tumor suppressor and negative regulator of the Ras signaling pathway [1][2]. Mutations in the NF1 gene frequently disrupt normal splicing patterns, leading to the inclusion of cryptic exons or the skipping of essential exons, which results in truncated or non-functional neurofibromin protein and causes Neurofibromatosis type 1 [3]. The term 'engineered complementary splice-regulatory sequence' refers to therapeutic agents, such as antisense oligonucleotides (ASOs), designed to hybridize with specific motifs within the NF1 pre-mRNA [4]. By binding to these sequences, the therapeutic agents can mask aberrant splice sites or recruit splicing machinery to correct the processing of the transcript [5]. This targeted approach aims to restore the production of functional neurofibromin, thereby mitigating the clinical manifestations of the disease, such as the development of neurofibromas and other associated malignancies [4][6]. This strategy represents a precision medicine approach for treating NF1 patients with specific splice-site mutations that are not amenable to traditional small-molecule therapies [5].

Other names

NF1 precursor mRNANeurofibromatosis type 1 pre-mRNANF1 transcriptNeurofibromin 1 primary transcript

Splice modulation via steric hindrance of splice sites or regulatory elements to restore correct mRNA reading frames or exclude deleterious pseudoexons.