High-dose AAV gene therapy deaths

  title={High-dose AAV gene therapy deaths},
  journal={Nature Biotechnology},
  pages={910 - 910}
  • Published 1 August 2020
  • Medicine
  • Nature Biotechnology

Low-dose AAV-CRISPR-mediated liver-specific knock-in restored hemostasis in neonatal hemophilia B mice with subtle antibody response

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.

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

Cross-species evolution of a highly potent AAV variant for therapeutic gene transfer and genome editing

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.

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?

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.

Changing trends in the development of AAV-based gene therapies: a meta-analysis of past and present therapies.

A meta-analysis was performed to identify factors that may inhibit the translation of therapeutic efficacy from preclinical large animal studies to first-in-human clinical trials and a detrimental effect on clinical efficacy was associated with alterations to administration routes.