Open research questions in CRISPR and Genetic Engineering
208 unresolved questions extracted from the limitations and future-work sections of 715 CRISPR and Genetic Engineering papers in our library. Each links back to the study that raised it.
What the literature leaves open
Further research is needed to understand the values that lead to views regarding HGGE, - Research on how values can be accurately collected is needed
Dutch Christian Faith Leaders Deliberating Human Germline Gene Editing: A Qualitative Study · 2026 · DOILittle research has been published on how values can be accurately collected. The importance of values is underlined, but there is a gap in understanding how to collect and analyze them.
Dutch Christian Faith Leaders Deliberating Human Germline Gene Editing: A Qualitative Study · 2026 · DOIThe study identifies the need for efficient TCR knockout in primary mouse T cells for preclinical immunotherapy research. The existing methods have limitations in terms of efficiency and toxicity. The study aims to address this gap by optimizing CRISPR-Cas9 RNP-based genome editing for T cells.
Optimizing CRISPR–Cas9-mediated TCR knockout in primary mouse CD8+, CD4+, and regulatory T cells · 2026 · DOIinvestigation of the range of defence systems that respond to phage infection by synthesising cyclic nucleotides to activate effectors, - exploration of the potential for Panoptes to work as a guard system
Cyclic tri-adenylate controls a CARF-TM effector in type II Panoptes anti-phage systems · 2026 · DOIThe lack of understanding of the type II Panoptes system and its mechanism of generating cyclic tri-adenylate. The need to investigate how the type II Panoptes system interacts with phages and provides defense against them. The gap in our understanding of the guard systems that constitute a fascinating component of the bacterial immune system.
Cyclic tri-adenylate controls a CARF-TM effector in type II Panoptes anti-phage systems · 2026 · DOIObservations stem from a single edited line, - Further evaluation of independent mutant lines or complementation assays is required, - Small sample size of 22 regenerated plants
CRISPR/Cas9-mediated FeS-ELF3 inactivation overcomes heteromorphic self-incompatibility in common buckwheat · 2026 · DOIFurther evaluation of independent mutant lines, - Complementation assays to definitively distinguish FeS-ELF3-specific pleiotropic effects, - Investigation of the effects of FeS-ELF3 inactivation on seed yield and plant architecture
CRISPR/Cas9-mediated FeS-ELF3 inactivation overcomes heteromorphic self-incompatibility in common buckwheat · 2026 · DOIsignificant recalcitrance to Agrobacterium-mediated transformation in watermelon, - limited CRISPR adoption in watermelon, - no specific numbers or percentages are given for many of the results
Molecular Targets and Trait Innovation in CRISPR-Edited Vegetable Crops: An Up-to-Date Review (2020–2026) · 2026 · DOIfurther research on CRISPR/Cas applications in vegetable crops, - exploration of salt tolerance mechanisms, - investigation of the potential of CRISPR/Cas13 system to confer resistance in RNA viruses
Molecular Targets and Trait Innovation in CRISPR-Edited Vegetable Crops: An Up-to-Date Review (2020–2026) · 2026 · DOIThe risk of off-target effects and non-specific genomic degradation. The potential for immune clearance or inflammatory responses in hosts. The need for careful optimization of design parameters, including guide RNA specificity, nuclease selection, and multiplex targeting strategies.
CRISPR-Cas systems as next-generation antimicrobials: a systemic review of mechanisms, delivery strategies, and translational challenges · 2026 · DOIMethodological heterogeneity - Risks of off-target effects that may inadvertently damage beneficial commensal bacteria and disrupt microbiome homeostasis - Uncertainties remain regarding biodistribution, pharmacokinetics, and long-term persistence of CRISPR reagents in vivo
CRISPR-Cas systems as next-generation antimicrobials: a systemic review of mechanisms, delivery strategies, and translational challenges · 2026 · DOIImmunological challenges associated with allogeneic HSC transplantation. Limited availability of well-matched donors for HSC transplantation. Technical challenges in gene editing approaches like CRISPR/Cas9.
Sickle cell disease: understanding pathophysiology, clinical features and advances in gene therapy approaches · 2025 · DOILimited understanding of effective gene therapy approaches for SCD. Need for alternative treatment options beyond allogeneic HSC transplantation. Gap in the development of gene editing approaches for SCD.
Sickle cell disease: understanding pathophysiology, clinical features and advances in gene therapy approaches · 2025 · DOIDevelopment of next-generation cellular immunotherapies, - Mechanistic studies in syngeneic models
Optimizing CRISPR–Cas9-mediated TCR knockout in primary mouse CD8+, CD4+, and regulatory T cells · 2026 · DOIHowever, integration with microfluidics for PoC applications is still poorly understood, despite CRISPR-Cas being widely used.
This article argues that the robust ethical reflection developed by the bioethics community to address human heritable genome editing can be used as a resource to address understudied questions of moral responsibility for anthropogenic insults to the germline.
Lipid nanoparticles (LNPs) are a promising nonviral delivery system for gene-editing proteins, but optimal formulations remain underexplored.
A multistep platform identifies spleen-tropic lipid nanoparticles for in vivo T cell–targeted delivery of gene-editing proteins · 2025 · DOIIn underrepresented populations, the mutational landscape and determinants of response to existing therapies are poorly characterized because of limited inclusion in clinical trials and studies.
Kinome-Focused CRISPR-Cas9 Screens in African Ancestry Patient-Derived Breast Cancer Organoids Identify Essential Kinases and Synergy of EGFR and FGFR1 Inhibition · 2025 · DOIGenome-editing technologies have enabled the clinical development of allogeneic cellular therapies, yet the optimal gene-editing modality for multiplex editing of therapeutic T cell product manufacturing remains elusive.
Quadruple adenine base–edited allogeneic CAR T cells outperform CRISPR/Cas9 nuclease–engineered T cells · 2025 · DOIHowever, the application of AI-based CRISPR modeling in plants is not yet fully explored.
AI-driven advances in plant biotechnology: sharpening the edge of plant tissue culture and genome editing · 2025 · DOIHowever, very little is known about the genetic machinery used by the fungus to infect and kill banana plants.
Optimization of a CRISPR-Cas9 in vitro protocol for targeting the SIX9 gene of Fusarium oxysporum f.sp. cubense race 1 associated with banana Fusarium wilt · 2025 · DOIHowever, reports vary widely describing Cas12 SNP sensitivity, and an underlying mechanism is lacking.
CRISPR-Cas9 genome editing has been extensively applied in both academia and clinical settings, but its genotoxic risks, including large insertions (LgIns), remain poorly studied due to methodological limitations.
Prevalent integration of genomic repetitive and regulatory elements and donor sequences at CRISPR-Cas9-induced breaks · 2025 · DOIWYL-domain containing transcription factors regulate fundamental processes in bacterial physiology, yet how these proteins sense cellular cues to elicit an allosteric response is not well understood.
Allosteric activation mechanism of DriD, a WYL-domain containing transcription regulator · 2025 · DOIHowever, the influence of alternative double-stranded break (DSB) repair pathways on knock-in remains to be fully explored.
Comparative analysis of multiple DNA double-strand break repair pathways in CRISPR-mediated endogenous tagging · 2025 · DOI
Most-cited papers in CRISPR and Genetic Engineering
- A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity · Science · 2012 · 15,745 citations
- Multiplex Genome Engineering Using CRISPR/Cas Systems · Science · 2013 · 14,247 citations
- RNA-Guided Human Genome Engineering via Cas9 · Science · 2013 · 8,551 citations
- The new frontier of genome engineering with CRISPR-Cas9 · Science · 2014 · 6,261 citations
- Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage · Nature · 2016 · 5,215 citations
- Genome-Scale CRISPR-Cas9 Knockout Screening in Human Cells · Science · 2013 · 4,984 citations
- Search-and-replace genome editing without double-strand breaks or donor DNA · Nature · 2019 · 4,538 citations
- CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity · Science · 2018 · 4,329 citations
- Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage · Nature · 2017 · 4,034 citations
- Nucleic acid detection with CRISPR-Cas13a/C2c2 · Science · 2017 · 3,740 citations
Most recent work
- CRISPR-on-Chip for Point-of-Care Diagnostics · ACS Nano · 2026
- Frequent, context-dependent effects of human genetic variation on Cas9 activity revealed by population-scale GUIDE-seq-2 and deep combinatorial CHANCE-seq profiling · bioRxiv · 2026
- Programmable genome editing in human cells using RNA-guided bridge recombinases · Science · 2026
- Structural modeling reveals phage proteins that manipulate bacterial immune signaling · Science · 2026
- CRISPR-Cas systems as next-generation antimicrobials: a systemic review of mechanisms, delivery strategies, and translational challenges · Frontiers in Microbiology · 2026
- Mammalian genome writing: Unlocking new length scales for genome engineering · Cell · 2026
- Rapid turnaround multiplex sequencing of SARS-CoV-2: comparing tiling amplicon protocol performance · medRxiv · 2026
- CRISPR-based diagnostics for infectious diseases: mechanisms, advancements and clinical transformation prospects · Frontiers in Cellular and Infection Microbiology · 2026
- A systematic survey of distal element-gene regulatory interactions with Direct-Capture Targeted Perturb-seq · bioRxiv · 2026
- CRISMER: A transformer-based Interpretable Deep Learning Approach for Genome-wide CRISPR Cas-9 Off-Target Prediction and Optimization · bioRxiv · 2026
Find a gap in your own CRISPR and Genetic Engineering sub-topic
This page shows what the CRISPR and Genetic Engineering literature already flags as unresolved. To narrow it to your specific question, run the guided finder — it searches the gap library on demand and checks candidates against 250M+ OpenAlex works.
Open the Research Gap Finder →