Prospects for gene replacement therapies in amyotrophic lateral sclerosis
- BiologyNature Reviews Neurology
The authors describe the current landscape of genetic therapies for ALS and discuss new opportunities for gene replacement therapy, focusing on loss-of-function mutations, as emerging evidence suggests genetic therapy as an attractive new therapeutic strategy for this disease.
Low-dose AAV-CRISPR-mediated liver-specific knock-in restored hemostasis in neonatal hemophilia B mice with subtle antibody response
- Biology, MedicineNature Communications
It is demonstrated that single dose of AAVs enabled long-term integration and expression of hF9 transgene in both adult and neonatal hemophilia B mice (mF9 −/−), yielding high levels of circulating human Factor IX and stable hemostasis restoration during entire 48-week observation period.
Episomes and Transposases—Utilities to Maintain Transgene Expression from Nonviral Vectors
This review addresses three prominent nonviral vector systems: the Sleeping Beauty transposase, S/MAR-based episomes, and viral plasmid replicon-based EBV vectors.
Age‐related macular degeneration: A disease of extracellular complement amplification
- Biology, MedicineImmunological reviews
The latest findings of complement activation in AMD are reviewed, in vivo observations made in human tissue, cellular models, the potential synergy of different AMD‐associated pathways are discussed, and current clinical trials and the future outlook are concluded.
Intrabiliary infusion of naked DNA vectors targets periportal hepatocytes in mice
- Biology, MedicineMolecular therapy. Methods & clinical development
Cross-species evolution of a highly potent AAV variant for therapeutic gene transfer and genome editing
- BiologyNature Communications
A highly potent new variant of AAV, AAV.cc47, is described with enhanced transduction efficiency over AAV serotype 9 and its efficacy is shown in different mouse models, pigs and non-human primates.
RNAi-mediated rheostat for dynamic control of AAV-delivered transgenes
This work presents a generalizable RNAi-based rheostat wherein AAV transgene expression is silenced using the clinically validated modality of chemically modified short interfering RNA (siRNA) conjugates or vectorized co-expression of short hairpin RNA (shRNA).
Direct ITR-to-ITR nanopore sequencing of AAV vector genomes.
- BiologyHuman gene therapy
It is found that the nanopore platform can cover the entirety of rAAV genomes from ITR to ITR without the need for pre-fragmentation, and nanopore sequencing can serve as a rapid and low-cost alternative for proofing AAV vectors.
Engineering Cancer Selective Virotherapies: Are the Pieces of the Puzzle Falling into Place?
- BiologyHuman gene therapy
A combination of improved delivery and selectivity, through novel capsids and promoters, coupled with more potent choices for the combinations of immunotherapy-based payloads seems capable of finally delivering innovative new gene therapies for oncology.