CRISPR Base & Prime Editing Pipeline — PatSnap Eureka
CRISPR Base Editing & Prime Editing: In Vivo Drug Pipeline
Base editing and prime editing enable single-nucleotide correction without double-strand DNA breaks or donor templates — making them uniquely suited for in vivo therapeutic application across sickle cell disease, DMD, CFTR, and retinal dystrophies.
Monogenic Diseases Addressed by Base & Prime Editing
The majority of disease-causing variants in ClinVar are point mutations or small indels — the precise correction class that base and prime editors are designed for, without DSBs or donor templates.
HBB & HEXA: Sickle Cell & Tay-Sachs
The sickle cell disease-causing A→T transversion in the HBB gene was the index therapeutic application of prime editing, demonstrated at Harvard University. HEXA deletion correction for Tay-Sachs established the benchmark for in vivo-applicable prime editing without DSBs or donor templates.
Most cited proof-of-concept targetCFTR F508del & R785*: Cystic Fibrosis
CFTR repair was demonstrated at efficiencies sufficient for functional rescue in intestinal and colonic organoids. Whole-genome sequencing of prime editing-repaired organoids showed no detectable off-target effects — a critical in vivo safety signal for IND filing, as reported from Hubrecht Institute/University Medical Center Utrecht.
Whole-genome WGS safety validatedDMD: Duchenne Muscular Dystrophy
Exons 9, 20, 35, 43, 55, and 61 of the DMD gene were targeted by prime editing for disease modeling and correction. Prime editing of six exonic sites in patient myoblasts achieved up to 28% desired editing with PE3. Nanoparticle-mediated correction of the dystrophin mutation in mice via HDR was also documented.
Up to 28% editing efficiency (PE3)Inherited Retinal Disease (IRD) Loci
Post-mitotic photoreceptors in the retina are identified as a critical in vivo target tissue specifically because these cells are inaccessible by ex vivo approaches. UT Southwestern Medical Center (2022) documented base and prime editors applied to IRD in preclinical research, referencing trajectory toward human clinical trials.
In vivo delivery mandatory — ex vivo impossibleGBA, LRRK2 & LMNA: Parkinson & Progeria
GBA and LRRK2 mutations (Parkinson disease) and LMNA (Hutchinson-Gilford progeria syndrome) were corrected in patient-derived iPSCs using PE3 augmented by p53 dominant-negative co-delivery, demonstrating that overcoming checkpoint responses is necessary for efficient editing in pluripotent stem cells.
p53DD co-delivery required for iPSCsTP53: Cancer Mutation Modeling & Correction
Common oncogenic TP53 point mutations were modeled in human organoids using prime editing, with efficiencies up to 97% in hepatocyte organoids. Nine cancer-associated TP53 mutations were modeled with up to 90% efficiency in human iPSCs using CBEs and ABEs. The dual use for modeling (gain-of-function installation) and correction (reversion) is consistently noted.
97% efficiency in hepatocyte organoidsFrom Cytosine Editors to Prime Editing Systems
Cytosine Base Editors (CBEs) fuse catalytically impaired Cas9 to a cytidine deaminase enzyme, enabling programmable C→T transitions within a defined editing window, without generating DSBs. High-precision CBEs using CDA1 truncation-nCas9 fusions have been reported, expanding targeting scope through alternative PAM-recognizing Cas9 variants. The Broad Institute described protein engineering strategies to minimize off-target activity (HF-BE3) and demonstrated RNP-based delivery for DNA-free base editing.
Adenine Base Editors (ABEs) catalyze A→G transitions — the mirror-image correction class to CBEs. Retrieved results indicate ABEs can target approximately 95.5% of clinically significant nonsense mutations accessible via the CRISPR-pass strategy. Off-target reduction engineering (V106W substitution, R153 deletion, Cas-embedding) has been applied in human embryonic stem cell contexts. Chemical modification of ABE mRNA and guide RNA enables robust in vivo editing in animal models.
Prime Editors (PEs) employ a fusion of Cas9H840A nickase with an engineered reverse transcriptase, directed by a pegRNA encoding both target site and desired edit. They support all 12 classes of point mutation, plus small insertions and deletions, without DSBs or donor templates. The evolution from PE2/PE3 to PE4/PE5 with MLH1 dominant-negative expression enhances substitution editing by 7.7-fold versus PE2. The PEmax architecture and Bi-PE strategy further push efficiency. PatSnap's life sciences intelligence platform tracks all major PE system advances across patents and literature.
CAR T Cell Base Editing documents the use of base editing in manufacturing next-generation adoptive cell therapies. The Charité Berlin group demonstrated combining nuclease-based CAR knock-in with CBE-mediated MHC class I and II knockout, reducing chromosomal translocations to 1.5% of edited cells. The Pin-point™ aptamer-mediated base editing platform (Rutgers University) enables simultaneous CAR transgene knock-in and multi-gene knockout in primary T cells with reduced translocation frequency.
Pipeline Metrics: Efficiency, Coverage & Disease Distribution
All data derived from patent filings and academic literature records retrieved via PatSnap Eureka. Values reflect published experimental results, not estimates.
Disease Area Coverage in Base & Prime Editing Pipeline
Distribution of therapeutic targets across disease categories based on retrieved patent and literature records via PatSnap Eureka.
In Vivo Delivery Platform Clinical Readiness
Relative clinical translation maturity of delivery platforms for base and prime editing therapeutics, based on retrieved evidence across patents and literature via PatSnap Eureka.
In Vivo Delivery Platforms & Emerging Combination Approaches
Safe and efficient in vivo delivery is consistently identified across retrieved results as the critical bottleneck for translating base and prime editing into systemic therapies.
| Platform / Approach | Mechanism | Key Evidence | Stage |
|---|---|---|---|
| AAV (Adeno-Associated Virus) | Viral vector; broad tropism, well-characterized serotypes, reduced immunogenicity. Size constraints require split-AAV or smaller Cas9 ortholog strategies. | Leading viral platform; documented across multiple retrieved results | Most advanced toward clinical translation |
| Lipid Nanoparticles (LNP) | Non-viral mRNA delivery; chemically modified mRNA-ABE shown to work in vivo in animal models (University of Massachusetts Medical School, 2020) | In vivo animal model data; avoids AAV integration risk | Advanced preclinical; most scalable in vivo format |
| Gold Nanoparticles (CRISPR-RNP) | Local injection of Cas9 RNP + donor DNA; corrected Duchenne dystrophin mutation in mice via HDR (UC Berkeley, 2017) | In vivo DMD mouse correction demonstrated | Preclinical |
| Poly(disulfide) Polymers | Glutathione-responsive degradable carriers for plasmid, mRNA, and RNP forms of CRISPR cargo; strong endosomal escape | Carrier design documented in retrieved literature | Preclinical |
| Exosome-Based (safeEXO) | Engineered exosomes co-delivering Cas9 RNP, sgRNA, ssDNA, and siRNA with organ-targeting capability (Columbia University, 2023) | In vivo gene editing with organ targeting demonstrated | Early preclinical; emerging direction |
| PE4/PE5 + MLH1dn (MMR Inhibition) | Transient MLH1 dominant-negative expression suppresses mismatch repair, enhancing substitution editing 7.7× vs PE2 (Princeton University, 2021) | Current benchmark PE architecture | Advanced preclinical; now standard for PE systems |
| HDAC Inhibitors + CBE/ABE | Small-molecule screen identified HDACi as enhancers of prime and base editing efficiency via UNG acetylation (West China Hospital, 2022) | Both CBE and ABE improved; product purity enhanced | Preclinical; pharmacological co-delivery paradigm |
| Vpx / SAMHD1 Degradation in HSPCs | Deoxynucleoside supplementation and SAMHD1 degradation address nucleotide metabolism bottlenecks in quiescent HSPCs (Dana-Farber Cancer Institute, 2023) | IND-enabling mechanistic work for blood disorder therapeutics | Preclinical; HSPC-specific solution |
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Who Is Driving Base & Prime Editing Innovation?
Innovation in this dataset is predominantly literature-driven (academic and institutional research) with a smaller but notable patent filing component from commercial entities. PatSnap Analytics maps the full assignee network.
Harvard / Broad Institute
Foundational base editing and prime editing publications, including the original BE1–BE3 editors and the 2019 prime editing Nature paper (Anzalone et al.). Multiple highly cited papers from this group anchor the entire field.
Princeton University
PE4/PE5/PEmax systems addressing MMR barriers to prime editing efficiency. The 2021 discovery that DNA mismatch repair actively opposes prime editing outcomes led to the current benchmark architecture.
Hubrecht Institute / UMC Utrecht
CFTR repair and TP53 modeling via prime editing in organoids, with whole-genome sequencing safety validation showing no detectable off-target effects — a critical dataset for IND filing.
New York Genome Center
Automated computational design of prime editors targeting more than 56,000 human pathogenic variants from ClinVar, with a public web portal (primeedit.nygenome.org) as direct clinical-translational infrastructure.
From Preclinical to IND-Enabling: Where the Field Stands
The Aarhus University review (2023) explicitly frames prime editing of HSPCs as a transition from ex vivo to in vivo CRISPR-based treatment of blood disorders, identifying pegRNA design for clinical targets and stem cell delivery vehicles as the two principal remaining challenges. This positions the field at an IND-enabling research stage for systemic administration.
CFTR-F508del functional repair in intestinal organoids with prime editing (Hubrecht Institute) provides a regulatory-relevant efficacy readout, with whole-genome sequencing demonstrating no detectable off-target events — a critical safety dataset for IND filing. Post-mitotic photoreceptors in the retina cannot be removed and edited ex vivo, making in vivo delivery mandatory for inherited retinal diseases, with UT Southwestern Medical Center referencing trajectory toward human clinical trials.
The dataset contains no records of approved base editing or prime editing drugs, and no retrieved results describe Phase II/III clinical data for these modalities. Multiple retrieved reviews reference ongoing CRISPR-based clinical trials broadly, though specific base editing/prime editing trials are not individually named in retrieved abstracts. PatSnap customers in pharma and biotech use Eureka to monitor clinical trial registrations in real time.
GBA and LMNA correction in patient-derived iPSCs using PE3 + p53DD (Sloan-Kettering, 2022) represents a disease modeling-to-correction translational arc relevant for cell therapy manufacturing. Dana-Farber Cancer Institute (2023) data that deoxynucleoside supplementation and SAMHD1 degradation improve prime editing in HSPCs constitutes IND-enabling mechanistic work for a systemic blood disorder therapeutic. The FDA itself contributed a review paper on CRISPR therapeutics emerging developments, reflecting regulatory awareness of this pipeline.
IP & Competitive Strategy for Base & Prime Editing
Derived from retrieved patent filings and academic literature. Use PatSnap's IP analytics to validate and extend these signals across your target landscape.
The Ex Vivo–to–In Vivo Transition Defines the Field
Retrieved results consistently identify in vivo delivery — particularly to stem cell compartments (HSPCs, neural progenitors) and post-mitotic tissues (retina, muscle, liver) — as the critical bottleneck. Organizations that solve this through LNP-mRNA, engineered AAV, or exosome platforms will hold the most valuable IP positions for in vivo base/prime editing therapeutics.
LNP + AAV most advanced toward clinical56,000+ ClinVar Variants Covered by Automated pegRNA Design
The New York Genome Center computational platform signals that the lead time advantage for any specific indication can be compressed to guide RNA design, shifting competitive advantage toward delivery, manufacturing, and clinical execution rather than target identification. The public portal (primeedit.nygenome.org) democratizes target access.
Competitive advantage shifts to delivery & manufacturingMMR Suppression & Pathway Co-Modulators Are Now Integral
PE4/PE5/PEmax and p53DD data indicate that efficient in vivo prime editing will likely require co-delivery of pathway modulators (MMR inhibitor mRNA, p53DD), increasing payload complexity but also creating IP space for combination product claims. These are not optional enhancements — they are core to system architecture.
Combination product IP space now openNovel Nuclease Scaffolds Signal Migration Away from SpCas9
Patent activity in novel CRISPR nuclease scaffolds (OMNI, α-synCas, Cpf1/Cas12a variants) signals that base and prime editing will migrate away from SpCas9 toward smaller, PAM-flexible, and potentially immunologically distinct orthologs suited for in vivo delivery size constraints and repeat dosing — a key consideration for IP freedom-to-operate analysis. PatSnap's trust-grade data supports FTO workflows.
FTO analysis critical for non-SpCas9 scaffoldsCRISPR Base Editing & Prime Editing — Key Questions Answered
Base editing and prime editing enable single-nucleotide correction without double-strand DNA breaks (DSBs) or exogenous donor templates. Conventional DSB-based CRISPR approaches address point mutations with low precision due to stochastic repair outcomes, whereas base and prime editors achieve programmable, predictable corrections — properties that make them uniquely suited for in vivo therapeutic application.
Retrieved results highlight sickle cell disease (HBB), cystic fibrosis (CFTR F508del and R785*), Duchenne muscular dystrophy (DMD exons 9, 20, 35, 43, 55, 61), Tay-Sachs disease (HEXA), alpha-1 antitrypsin deficiency (A1AT), Parkinson disease (GBA, LRRK2), Hutchinson-Gilford progeria syndrome (LMNA), and inherited retinal diseases as key therapeutic targets.
Safe and efficient in vivo delivery is consistently identified across retrieved results as the critical bottleneck. Key platforms include AAV (leading viral platform), lipid nanoparticles (LNPs) for mRNA-encoded editors, gold nanoparticles, poly(disulfide) polymers, and exosome-based delivery. LNP and AAV approaches are most advanced toward clinical translation.
Prime editing employs a fusion of Cas9H840A nickase with an engineered reverse transcriptase, directed by a prime editing guide RNA (pegRNA) that encodes both the target site and the desired edit. It supports all 12 classes of point mutation, as well as small insertions and deletions, without DSBs or donor templates. CBEs enable C→T transitions and ABEs enable A→G transitions, each limited to their respective conversion class.
Key optimization advances include bi-directional prime editing (Bi-PE) increasing efficiency up to 16-fold, PE4/PE5 systems with MLH1 dominant-negative expression enhancing substitution editing by 7.7-fold versus PE2, HDAC inhibitors identified as enhancers of prime and base editing efficiency, and p53DD co-delivery significantly enhancing efficiencies in human pluripotent stem cells.
The dataset contains no records of approved base editing or prime editing drugs, and no retrieved results describe Phase II/III clinical data for these modalities. The field is positioned at an IND-enabling research stage for systemic administration, with ex vivo HSPC editing approaching clinical readiness and in vivo delivery solutions still in development.
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References
- Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage — Howard Hughes Medical Institute / Harvard University, 2016
- Search-and-replace genome editing without double-strand breaks or donor DNA — Harvard University (Anzalone et al.), 2019
- Prime editing in hematopoietic stem cells — From ex vivo to in vivo CRISPR-based treatment of blood disorders — Aarhus University, 2023
- Evaluating CRISPR-based prime editing for cancer modeling and CFTR repair in organoids — Hubrecht Institute / University Medical Center Utrecht, 2021
- Automated design of CRISPR prime editors for 56,000 human pathogenic variants — New York Genome Center, 2021
- Enhanced prime editing systems by manipulating cellular determinants of editing outcomes — Princeton University, 2021
- Transient inhibition of p53 enhances prime editing and cytosine base-editing efficiencies in human pluripotent stem cells — Sloan-Kettering Institute for Cancer Research, 2022
- Base and Prime Editing in the Retina — From Preclinical Research toward Human Clinical Trials — UT Southwestern Medical Center, 2022
- Nucleotide metabolism constrains prime editing in hematopoietic stem and progenitor cells — Dana-Farber Cancer Institute, 2023
- CRISPR-pass: Gene rescue of nonsense mutations using adenine base editors — Seoul National University, 2019
- Chemical modifications of adenine base editor mRNA and guide RNA expand its application scope — University of Massachusetts Medical School, 2020
- Bi-PE: bi-directional priming improves CRISPR/Cas9 prime editing in mammalian cells — West China Hospital, Sichuan University, 2022
- HDAC inhibitors improve CRISPR-Cas9 mediated prime editing and base editing — West China Hospital, Sichuan University, 2022
- CRISPR-Cas9 DNA Base-Editing and Prime-Editing — Oxford University Hospitals NHS Foundation Trust, 2020
- Base and Prime Editing Technologies for Blood Disorders — INSERM UMR 1163 / Imagine Institute, Paris, 2021
- High-precision CRISPR-Cas9 base editors with minimized bystander and off-target mutations — Massachusetts General Hospital / Harvard, 2018
- Combining different CRISPR nucleases for simultaneous knock-in and base editing prevents translocations in multiplex-edited CAR T cells — Charité – Universitätsmedizin Berlin, 2022
- An aptamer-mediated base editing platform for simultaneous knock-in and multiple gene knockout for allogeneic CAR-T cells generation — Rutgers University, 2023
- Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA in vivo induces homology-directed DNA repair — UC Berkeley, 2017
- Tissue-Specific Delivery of CRISPR Therapeutics: Strategies and Mechanisms of Non-Viral Vectors — Hamad Bin Khalifa University, 2020
- ClinVar — NCBI National Center for Biotechnology Information (pathogenic variant database referenced throughout)
- Broad Institute — Base editing foundational research (HF-BE3, RNP-based delivery)
- U.S. Food and Drug Administration — Review of CRISPR therapeutics emerging developments and clinical applications
All data and statistics on this page are sourced from the references above and from PatSnap's proprietary innovation intelligence platform. This report is derived from a limited set of patent and literature records and represents a snapshot of innovation signals within this dataset only.
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