{
  "id": 19648888,
  "title": "Engineering a High-Fidelity CRISPR-Cas13d System for Targeted RNA Depletion in Plasmodium falciparum",
  "url": "https://urgent.news/2026/11/12/engineering-a-high-fidelity-crispr-cas13d-system-for-targeted-rna",
  "topic": "science",
  "section": "Science",
  "published": "2026-11-12T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.11.09.765308v1?rss=1"
  },
  "original_language": "en",
  "account": "In a significant advancement for malaria research, scientists have developed a precise RNA-depletion system targeting Plasmodium falciparum, the parasite responsible for the most lethal form of malaria. This innovative approach, utilizing a high-fidelity Cas13d (HF-RfxCas13d), addresses limitations encountered in functional genomics due to the parasite's evolutionary lack of an endogenous RNA interference pathway.\n\nBy strategically integrating the HF-RfxCas13d expression cassette at the dispensable pfs47 locus, researchers created a stable transgenic line with constitutive cytosolic expression of HF-RfxCas13d. This development allowed for gene silencing without compromising the parasite's ability to grow and reproduce within host erythrocytes.\n\nThe researchers employed CRISPR-SpyCas9 to introduce single or dual guide RNAs (gRNAs) targeting three endogenous loci—ap4, ap2-exp, and ap2-g. This approach led to substantial mRNA depletion (ranging from 41% to 76%) of the targeted genes, offering a powerful tool for functional genomics in P. falciparum.\n\nThe system's application to the master transcriptional regulator of gametocytogenesis (ap2-g) showcased its potential. Depletion of ap2-g functionally impaired sexual differentiation in committed parasites, resulting in a notable 70% reduction in Sexual Conversion Rate. This breakthrough could accelerate the identification of potential drug targets and streamline malaria research efforts, providing a scalable and non-locus-modifying addition to the genetic toolbox for studying P. falciparum.",
  "summary": "Functional genomics in Plasmodium falciparum is severely constrained by the evolutionary absence of an endogenous RNA interference pathway and the requirement for time-consuming direct target locus modification by conventional conditional genetic engineering systems. To overcome these limitations, we established a programmable post-transcriptional gene silencing system in P. falciparum using…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}