Emerging applications of gene editing technologies for the development of climate-resilient crops DOI Creative Commons
R. L. Chavhan,

Siddhant Gahininath Jaybhaye,

V. R. Hinge

et al.

Frontiers in Genome Editing, Journal Year: 2025, Volume and Issue: 7

Published: March 10, 2025

Climate change threatens global crop yield and food security due to rising temperatures, erratic rainfall, increased abiotic stresses like drought, heat, salinity. Gene editing technologies, including CRISPR/Cas9, base editors, prime offer precise tools for enhancing resilience. This review explores the mechanisms of these technologies their applications in developing climate-resilient crops address future challenges. While CRISPR/enables targeted modifications plant DNA, editors allow direct conversion without inducing double-stranded breaks, enable insertions, deletions, substitutions. By understanding manipulating key regulator genes involved stress responses, such as DREB, HSP, SOS, ERECTA, HsfA1, NHX; tolerance can be enhanced against salt stress. improve traits related root development, water use efficiency, response pathways, heat shock response, photosynthesis, membrane stability, ion homeostasis, osmotic adjustment, oxidative response. Advancements gene integration with genomics, phenomics, artificial intelligence (AI)/machine learning (ML) hold great promise. However, challenges off-target effects, delivery methods, regulatory barriers must addressed. highlights potential develop crops, contributing sustainable agriculture.

Language: Английский

Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions DOI Creative Commons

Peilin Lu,

Dongxue Ruan,

Meiqi Huang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: July 1, 2024

The applications of hydrogels have expanded significantly due to their versatile, highly tunable properties and breakthroughs in biomaterial technologies. In this review, we cover the major achievements potential therapeutic applications, focusing primarily on two areas: emerging cell-based therapies promising non-cell modalities. Within context cell therapy, discuss capacity overcome existing translational challenges faced by mainstream therapy paradigms, provide a detailed discussion advantages principal design considerations for boosting efficacy as well list specific examples different disease scenarios. We then explore drug delivery, physical intervention therapies, other areas (e.g., bioadhesives, artificial tissues, biosensors), emphasizing utility beyond mere delivery vehicles. Additionally, complement our latest progress clinical application outline future research directions, particularly terms integration with advanced biomanufacturing This review aims present comprehensive view critical insights into selection both tailored meet requirements diverse diseases situations.

Language: Английский

Citations

83
Principles of CRISPR-Cas9 technology: Advancements in genome editing and emerging trends in drug delivery DOI Creative Commons
Alaa A. A. Aljabali, Mohamed El‐Tanani, Murtaza M. Tambuwala

et al.

Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: 92, P. 105338 - 105338

Published: Jan. 6, 2024

The rapid advancement of CRISPR-Cas9 technology has instigated a profound transformation in genome editing with significant implications for fields like health, agriculture, and biotechnology. This abstract provides an overview the historical significance fundamental components CRISPR-Cas9, notably Cas9 protein guide RNA, underscoring its pivotal role genetic manipulation. It emphasizes CRISPR-Cas9's preeminence domain precise editing, driving breakthroughs personalized medicine, gene therapy, agriculture. Of paramount importance is integration nanomaterials, encompassing lipid-based polymeric nanoparticles, alongside viral vectors, serving as potent vehicles augmenting delivery efficiency precision. We explore strategies aimed at enhancing through while also addressing ethical regulatory considerations. In expert opinion section, we offer nuanced perspective on present state field, highlighting potential transformative progress research therapy. stands brink unlocking new possibilities providing innovative solutions to address pressing global challenges.

Language: Английский

Citations

39
Recent Advancements in Reducing the Off-Target Effect of CRISPR-Cas9 Genome Editing DOI Creative Commons
Misganaw Asmamaw Mengstie,

Muluken Teshome Azezew,

Tadesse Asmamaw Dejenie

et al.

Biologics, Journal Year: 2024, Volume and Issue: Volume 18, P. 21 - 28

Published: Jan. 1, 2024

Abstract: The CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)) and the associated protein (Cas9) system, a young but well-studied genome-editing tool, holds plausible solutions to wide range of genetic disorders. single-guide RNA (sgRNA) with 20-base user-defined spacer sequence Cas9 endonuclease form core CRISPR-Cas9 system. This sgRNA can direct nuclease any genomic region that includes protospacer adjacent motif (PAM) just downstream matches sequence. current challenge in clinical applications technology is potential off-target effects cause DNA cleavage at incorrect sites. Off-target genome editing confuses diminishes therapeutic addition potentially casting doubt on scientific findings regarding activities genes. In this review, we summarize recent technological advancements reducing effect editing. Keywords: CRISPR-Cas9, editing, effect, advancements, review

Language: Английский

Citations

26
Focused ultrasound gene delivery for the treatment of neurological disorders DOI Open Access
Rikke Hahn Kofoed, Isabelle Aubert

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(3), P. 263 - 277

Published: Jan. 11, 2024

Language: Английский

Citations

20
CAR-T cell manufacturing landscape—Lessons from the past decade and considerations for early clinical development DOI Creative Commons
Juliana Dias,

John García,

Giulia Agliardi

et al.

Molecular Therapy — Methods & Clinical Development, Journal Year: 2024, Volume and Issue: 32(2), P. 101250 - 101250

Published: April 16, 2024

CAR-T cell therapies have consolidated their position over the last decade as an effective alternative to conventional chemotherapies for treatment of a number hematological malignancies. With exponential increase in commercial and hundreds phase 1 trials exploring efficacy different settings (including autoimmunity solid tumors), demand manufacturing capabilities recent years has considerably increased. In this review, we explore current landscape discuss some challenges limiting production capacity worldwide. We describe latest technical developments GMP platform design facilitate delivery range increasingly complex products, associated with translation new scientific into clinical products patients. all aspects process, namely early development, technology, quality control, requirements industrial scaling. Finally, faced small academic team, responsible high innovative our experience setup bench-to-clinic pipeline, streamlined workflow, implementation diverse portfolio trials.

Language: Английский

Citations

18
Current approaches to develop “off-the-shelf” chimeric antigen receptor (CAR)-T cells for cancer treatment: a systematic review DOI Creative Commons
Cristina Aparicio, Carlos Acebal, Margarita González‐Vallinas

et al.

Experimental Hematology and Oncology, Journal Year: 2023, Volume and Issue: 12(1)

Published: Aug. 21, 2023

Chimeric antigen receptor (CAR)-T cell therapy is one of the most promising advances in cancer treatment. It based on genetically modified T cells to express a CAR, which enables recognition specific tumour interest. To date, CAR-T therapies approved for commercialisation are designed treat haematological malignancies, showing impressive clinical efficacy patients with relapsed or refractory advanced-stage tumours. However, since they all use patient´s own as starting material (i.e. autologous use), have important limitations, including manufacturing delays, high production costs, difficulties standardising preparation process, and failures due patient dysfunction. Therefore, many efforts currently being devoted contribute development safe effective allogeneic use, should be overcome risks entail: immune rejection graft-versus-host disease (GvHD). This systematic review brings together wide range different approaches that been studied achieve discuss advantages disadvantages every strategy. The methods were classified two major categories: those involving extra genetic modifications, addition CAR integration, relying selection alternative sources/subpopulations γδ cells, induced pluripotent stem (iPSCs), umbilical cord blood memory subpopulations, virus-specific cytokine-induced killer cells). We observed that, although modification widely used approach, new combining both emerged. more preclinical research needed determine appropriate strategy bring this antitumour setting.

Language: Английский

Citations

37
CRISPR/Cas9-mediated genome editing techniques and new breeding strategies in cereals – current status, improvements, and perspectives DOI Creative Commons
Sunny Ahmar, Göetz Hensel, Damian Gruszka

et al.

Biotechnology Advances, Journal Year: 2023, Volume and Issue: 69, P. 108248 - 108248

Published: Sept. 2, 2023

Cereal crops, including triticeae species (barley, wheat, rye), as well edible cereals (wheat, corn, rice, oat, rye, sorghum), are significant suppliers for human consumption, livestock feed, and breweries. Over the past half-century, modern varieties of cereal crops with increased yields have contributed to global food security. However, presently cultivated elite crop were developed mainly optimal environmental conditions. Thus, it has become evident that taking into account ongoing climate changes, currently a priority should be given developing new stress-tolerant cultivars. It is necessary enhance accuracy methods time required generate cultivars desired features adapt change keep up world population expansion. The CRISPR/Cas9 system been powerful versatile genome editing tool achieve desirable traits, such high-yielding, stress-tolerant, disease-resistant transgene-free lines in major cereals. Despite recent advances, application faces several challenges, amount develop lines, laboriousness, limited number genotypes may used transformation vitro regeneration. Additionally, through restricted many countries, especially Europe New Zealand, due lack flexibility GMO regulations. This review provides comprehensive update researchers interested improving using gene-editing technologies, CRISPR/Cas9. We will some critical studies on improvements their contributing factors superior technologies.

Language: Английский

Citations

29
Evolution of CRISPR/Cas Systems for Precise Genome Editing DOI Open Access
Magdalena Hryhorowicz, Daniel Lipiński, Joanna Zeyland

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(18), P. 14233 - 14233

Published: Sept. 18, 2023

The bacteria-derived CRISPR/Cas (an acronym for regularly interspaced short palindromic repeats/CRISPR-associated protein) system is currently the most widely used, versatile, and convenient tool genome engineering. CRISPR/Cas-based technologies have been applied to disease modeling, gene therapies, transcriptional modulation, diagnostics. Nevertheless, some challenges remain, such as risk of immunological reactions or off-target effects. To overcome these problems, many new methods tools developed. In this review, we describe current classification CRISPR systems precise genome-editing technologies, summarize latest applications technique in several fields research, and, finally, discuss limitations, ethical issues, challenges.

Language: Английский

Citations

27
Beyond the promise: evaluating and mitigating off-target effects in CRISPR gene editing for safer therapeutics DOI Creative Commons
Rui Lopes,

Megana Prasad

Frontiers in Bioengineering and Biotechnology, Journal Year: 2024, Volume and Issue: 11

Published: Jan. 18, 2024

Over the last decade, CRISPR has revolutionized drug development due to its potential cure genetic diseases that currently do not have any treatment. was adapted from bacteria for gene editing in human cells 2012 and, remarkably, only 11 years later seen it’s very first approval as a medicine treatment of sickle cell disease and transfusion-dependent beta-thalassemia. However, application systems is associated with unintended off-target on-target alterations (including small indels, structural variations such translocations, inversions large deletions), which are source risk patients vital concern safe therapies. In recent years, wide range methods been developed detect unwanted effects CRISPR-Cas nuclease activity. this review, we summarize different assessment, discuss their strengths limitations, highlight strategies improve safety systems. Finally, relevance pre-clinical assessment therapeutics within current regulatory context.

Language: Английский

Citations

13
Application of multiple sgRNAs boosts efficiency of CRISPR/Cas9-mediated gene targeting in Arabidopsis DOI Creative Commons
Jing Li, Dali Kong, Yongping Ke

et al.

BMC Biology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 17, 2024

Abstract Background Precise gene targeting (GT) is a powerful tool for heritable precision genome engineering, enabling knock-in or replacement of the endogenous sequence via homologous recombination. We recently established CRISPR/Cas9-mediated approach GT in Arabidopsis thaliana (Arabidopsis) and rice reported that double-strand breaks (DSBs) frequency Cas9 influences efficiency. However, relationship between DSBs at same locus was not examined. Furthermore, it has never been investigated whether an increase number copies sgRNAs use multiple would improve efficiency GT. Results Here, we achieved precise loci Embryo Defective 2410 ( EMB2410 ) Repressor Silencing 1 ROS1 using sequential transformation strategy combination sgRNAs. show increasing copy elevates both On other hand, application does always enhance Our results also suggested some inefficient play role as helper to facilitate activity. Conclusions The this study clearly DSB efficiency, rather than mutation pattern, one most important key factors determining This provides new insights into sgRNAs, DSBs, GTs molecular mechanisms plants.

Language: Английский

Citations

12