In vivo prime editing rescues photoreceptor degeneration in nonsense mutant retinitis pigmentosa.

The next-generation gene editing tool, prime editing (PE), is adept at correcting point mutations precisely with high editing efficiency and rare off-target events and shows promising therapeutic value in treating hereditary diseases. Retinitis pigmentosa (RP) is the most common type of inherited retinal dystrophy and is characterized by progressive degeneration of retinal photoreceptors and, consequently, visual decline. To date, effective treatments for RP are lacking.

Aurora A Kinase Inhibition Is Synthetic Lethal With the Activation of MYCN in Retinoblastoma.

Purpose: RB1 inactivation and MYCN activation have been documented as common oncogenic alterations in retinoblastoma (RB). Direct targeting of RB1 and MYCN has not yet been proven to be feasible. The current treatment options for RB mainly consist of conventional chemotherapy, which inevitably poses health-threatening side effects.

A Penetrable AAV2 Capsid Variant for Efficient Intravitreal Gene Delivery to the Retina.

Purpose: This study aimed to identify a novel recombinant adeno-associated virus (rAAV) capsid variant that can widely transfect the deep retina through intravitreal injection and to assess their effectiveness and safety in gene delivery.

Methods: By adopting the sequences of various cell-penetrating peptides and inserting them into the capsid modification region of AAV2, we generated several novel variants. The green fluorescent protein (GFP)-carrying variants were screened following intravitreal injection.

Circulating Tumor DNA in Conjunctival Melanoma: Landscape and Surveillance Value.

Purpose: To evaluate the surveillance value of circulating tumor DNA (ctDNA) for detecting distant metastasis and indicating systemic therapeutic efficacy in conjunctival melanoma (CoM).

Design: Retrospective, observational case series.

Methods: From July 2021 to June 2023, 30 CoM patients in our center underwent plasma ctDNA assessment, out of which 12 individuals presented with distant metastases.

Single-cell sequencing depicts tumor architecture and empowers clinical decision in metastatic conjunctival melanoma.

Conjunctival melanoma (CoM) is a potentially devastating tumor that can lead to distant metastasis. Despite various therapeutic strategies for distant metastatic CoM, the clinical outcomes remain unfavorable. Herein, we performed single-cell RNA sequencing (scRNA-seq) of 47,017 cells obtained from normal conjunctival samples (n = 3) and conjunctival melanomas (n = 7).

High-risk histopathologic features in local advanced conjunctival melanoma.

Purpose: To identify high-risk histopathologic and molecular features of local recurrence, nodal metastasis, distant metastasis (DM) and disease-specific death (DSD) in conjunctival melanoma (CoM).

Methods: Ninety patients with pathologically diagnosed CoM between 2008 and 2023 were enrolled. Immunohistochemistry staining of BRAF, NRAS, CD117, PD-1 and PD-L1 was performed in 65 and 45 patients, respectively.

Genetic landscape and prognosis of conjunctival melanoma in Chinese patients.

Aims: Conjunctival melanoma (CoM) is a rare but highly lethal ocular melanoma and there is limited understanding of its genetic background. To update the genetic landscape of CoM, whole-exome sequencing (WES) and targeted next-generation sequencing (NGS) were performed.

Methods: Among 30 patients who were diagnosed and treated at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, from January 2018 to January 2023, WES was performed on 16 patients, while targeted NGS was conducted on 14 patients.

The Use of rAAV2-RB1-Mediated Gene Therapy in Retinoblastoma.

Purpose: Retinoblastoma (RB) is a life-threatening malignancy that arises from the retina and is activated upon homozygous inactivation of the tumor suppressor RB1. Gene therapy targeting RB1 is an effective strategy to treat RB. However, it is difficult to target the RB1 gene by site-specific repair, with up to 3366 gene mutation sites identified in RB1.

Risk factors and prognosis of orbital exenteration in conjunctival melanoma.

Objectives: To identify the risk factors of orbital exenteration and to evaluate the prognosis of exenterated patients with conjunctival melanoma (CM).

Methods: 79 consecutive CM patients treated at our centre from January 2000 to September 2021 were included. The demographic, clinical and pathological characteristics were compared between eye-sparing patients and orbital exenteration patients.

Biophysics Role and Biomimetic Culture Systems of ECM Stiffness in Cancer EMT.

Oncological diseases have become the second leading cause of death from noncommunicable diseases worldwide and a major threat to human health. With the continuous progress in cancer research, the mechanical cues from the tumor microenvironment environment (TME) have been found to play an irreplaceable role in the progression of many cancers. As the main extracellular mechanical signal carrier, extracellular matrix (ECM) stiffness may influence cancer progression through biomechanical transduction to modify downstream gene expression, promote epithelial-mesenchymal transition (EMT), and regulate the stemness of cancer cells.

American Joint Committee on Cancer Tumor Staging System Predicts the Outcome and Metastasis Pattern in Conjunctival Melanoma.

Purpose: To assess the predictive value of the tumor staging system in the AJCC Cancer Staging Manual, Eighth Edition, and histologic features for outcomes and metastasis patterns in conjunctival melanoma (CM).

Design: Retrospective, single-center cohort study.

Participants: Eighty-three patients with CM were treated at Shanghai Ninth People's Hospital between 2000 and 2021.

Regulation of epigenetic homeostasis in uveal melanoma and retinoblastoma.

Uveal melanoma (UM) and retinoblastoma (RB), which cause blindness and even death, are the most frequently observed primary intraocular malignancies in adults and children, respectively. Epigenetic studies have shown that changes in the epigenome contribute to the rapid progression of both UM and RB following classic genetic changes. The loss of epigenetic homeostasis plays an important role in oncogenesis by disrupting the normal patterns of gene expression.

mA RNA hypermethylation-induced BACE2 boosts intracellular calcium release and accelerates tumorigenesis of ocular melanoma.

Ocular melanoma, including uveal melanoma (UM) and conjunctival melanoma (CM), is the most common and deadly eye cancer in adults. Both UM and CM originate from melanocytes and exhibit an aggressive growth pattern with high rates of metastasis and mortality. The integral membrane glycoprotein beta-secretase 2 (BACE2), an enzyme that cleaves amyloid precursor protein into amyloid beta peptide, has been reported to play a vital role in vertebrate pigmentation and metastatic melanoma.

Novel insight into the regulatory roles of diverse RNA modifications: Re-defining the bridge between transcription and translation.

RNA modifications can be added or removed by a variety of enzymes that catalyse the necessary reactions, and these modifications play roles in essential molecular mechanisms. The prevalent modifications on mRNA include N6-methyladenosine (mA), N1-methyladenosine (mA), 5-methylcytosine (mC), 5-hydroxymethylcytosine (hmC), pseudouridine (Ψ), inosine (I), uridine (U) and ribosemethylation (2'-O-Me). Most of these modifications contribute to pre-mRNA splicing, nuclear export, transcript stability and translation initiation in eukaryotic cells.