16 papers · ranked by Valyu relevance
Wei-Kai Hua, Jeff C. Hsu, Yi-Chun Chen, Peter S. Chang + 6 more
Recent advances in gene therapy have brought novel treatment options for cancer. However, the full potential of this approach has yet to be unlocked due to the safety concerns and limited payload capacity of commonly utilized viral vectors. Virus-free DNA transposons, including piggyBac, have potential to obviate these…
Rohini Prakash, Roderick Slavcev
Gene therapy offers immense potential for treating various diseases, including cancer, immunodeficiencies, and cardiovascular conditions. The efficacy of gene therapy (GT) largely depends on the vector used for gene delivery. Viral vectors, while effective, pose risks including insertional mutagenesis, immune…
Jonas Kolibius, Fabian Weiss, Patrick C. Freitag, Andreas Plückthun
High-capacity adenoviral (HC-AdV) vectors offer large transgene capacities and long-term expression of therapeutics, but require high doses due to limited transgene expression. In contrast, replication-competent AdV (RC-AdV) vectors enhance in situ transgene expression by genome replication and increased transcription…
Andrés Ramos-Valle, Henning Kirst, Mónica L. Fanarraga
Targeting, safety, scalability, and storage stability of vectors are still challenges in the field of nucleic acid delivery for gene therapy. Silica-based nanoparticles have been widely studied as gene carriers, exhibiting key features such as biocompatibility, simplistic synthesis and enabling easy surface…
Carsten T. Charlesworth, Shota Homma, Fabian Suchy, Sicong Wang + 7 more
A multitude of tools now exist that allow us to precisely manipulate the human genome in a myriad of different ways. However, successful delivery of these tools to the cells of human patients remains a major barrier to their clinical implementation. Here we introduce a new cellular approach for in vivo genetic…
Nikoletta Psatha, Pavel Sova, Grigorios Georgolopoulos, Kiriaki Paschoudi + 12 more
Regulation of gene expression during cell development and differentiation is chiefly orchestrated by distal noncoding regulatory elements that precisely modulate cell selective gene activity. Gene therapy vectors rely on the cellular and context specificity of regulatory DNA elements to express therapeutic transgenes…
Jicong Cao, Eva Maria Novoa, Zhizhuo Zhang, William C.W. Chen + 6 more
Despite significant clinical progress in cell and gene therapies, maximizing protein expression in order to enhance potency remains a major challenge. One approach to increase protein expression is by optimizing translation through the engineering of 5’ untranslated regions (5’ UTRs). Here, we developed a…
Austin Hartman, Oliver Takacsi-Nagy, Courtney Kernick, Nicole E. Theberath + 17 more
Evolution simultaneously and combinatorially explores complex genetic changes across perturbation classes, including gene knockouts, knockdowns, overexpression, and the creation of new genes from existing domains. Separate technologies are capable of genetic perturbations at scale in human cells, but these methods are…
Khishigjargal Batjargal, Tomoki Togashi, Yuji Kashiwakura, Nemekhbayar Baatartsogt + 8 more
Gene knock-in therapy has the potential to cure inherited liver diseases but is limited by low efficiency and delivery complexity. Here, we developed a single adeno-associated virus (AAV) vector system comprising a compact CRISPR effector, enAsCas12f, a guide RNA, and a donor template to enable therapeutic genome…
Yan Qi, Xianghua Zhang, Janae Wheeler Cull, Charles Wall + 2 more
Gene transfer (GT) vectors have diverse applications. They have been used to restore cellular activities by reconstituting normal cellular functions, by delivering therapeutic compounds, and by priming immune responses as genetic vaccines. Viruses, nature’s gene delivery vehicles, have formed the basis of most GT…
Liming Luo, Jocelyn Duen-Ya Jea, Yan Wang, Pei-Wen Chao + 1 more
The ability to control the expression of a therapeutic gene or a transgene in mammalian cells is crucial for safe and efficacious gene and cell therapy, as well as for elucidating the function of a specific gene product. Yet current mammalian gene regulation systems either evoke harmful immune responses in hosts or…
Raed Ibraheim, Chun-Qing Song, Aamir Mir, Nadia Amrani + 2 more
Clustered, regularly interspaced, short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) have recently opened a new avenue for gene therapy. Cas9 nuclease guided by a single-guide RNA (sgRNA) has been extensively used for genome editing. Currently, three Cas9 orthologs have been adapted for in vivo…
Navneet Matharu, Sawitree Rattanasopha, Lenka Maliskova, Yi Wang + 3 more
Haploinsufficiency, having only one functional copy of a gene, leads to a wide range of human disease and has been associated with over 300 genes. Here, we tested whether CRISPR activation (CRISPRa) could rescue a haploinsufficient disease in vivo. Haploinsufficiency of Sim1, a transcription factor involved in the…
Pingjuan Li, Benjamin P. Kleinstiver, Mihoko Y. Leon, Michelle S. Prew + 5 more
No effective treatment exists for dominant inherited diseases. Here, we present a CRISPR/Cas9 genome editing strategy that combines multiple innovations to achieve specific and efficient disruption of the pathogenic allele with a single-nucleotide mutation (Rho-P23H) in a mouse model of dominant retinitis pigmentosa.…
Qiaorui Yao, Zhuangjie Lin, Keyuan Lai, Xianying Zeng + 3 more
Synthetic CRISPR-Cas9 gene drive has been developed as a potential tool to control harmful species. However, Cas9 gene drive faces high resistance rate and mitigation strategies developed so far are difficult to implement. Furthermore, studying the resistance to gene drive is time consuming and challenging in higher…
Marilena De Almeida, Jonathan M. Henshaw, Adam G. Jones, Xiaoyan Long
Artificial gene drives offer a promising approach for controlling populations of agricultural pests, invasive species and disease vectors, such as malaria-carrying mosquitoes. Gene-drive alleles induce a transmission bias, meaning there is a greater than 50% probability that they will be inherited by offspring…