Related Experiment Video
Updated: May 20, 2025
07:09
Development of Efficient OLEDs from Solution Deposition
Published on: November 4, 2022
2.0K
Highly efficient in vivo hematopoietic stem cell transduction using an optimized self-complementary adeno-associated
Carsten T Charlesworth1, Shota Homma1,2, Anais K Amaya3
1Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Lorry I. Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA.
Molecular Therapy. Methods & Clinical Development
|March 25, 2025
Summary
Optimizing adeno-associated virus serotype 6 (AAV6) vectors for in vivo gene therapy in hematopoietic stem cells (HSCs) is crucial. This study found second-strand synthesis limits HSC transduction, but AAV6 shows promise for treating blood disorders.
Area of Science:
- Gene Therapy
- Hematology
- Molecular Biology
Background:
- In vivo gene therapy offers potential for hematological diseases.
- Hematopoietic stem cells (HSCs) are key targets for gene therapy.
Purpose of the Study:
- To optimize adeno-associated virus serotype 6 (AAV6) vector parameters for effective in vivo HSC transduction.
- To identify limitations and enhance transgene expression in HSCs.
Main Methods:
- Systematic optimization of AAV6 vector genetic architectures and delivery methods.
- Evaluation of Cre recombination efficiency in immunophenotypic HSCs.
- Assessment of HSC accessibility and transduction preference in bone marrow.
Main Results:
- An optimized AAV6 protocol achieved functional recombination in over two-thirds of HSCs.
- Second-strand synthesis was identified as a critical factor limiting transgene expression.
- HSCs in bone marrow are accessible for transduction without mobilization, showing a preference for transduction over other bone marrow cells.
Conclusions:
- AAV6 vectors demonstrate significant potential for in vivo HSC gene therapy.
- Findings provide a foundation for developing AAV-based and alternative in vivo HSC gene therapies.
- Understanding transduction limitations is key for improving gene therapy efficacy.
Related Concept Videos
01:07Catalytically Perfect Enzymes
3.8K
The theory of catalytically perfect enzymes was first proposed by W.J. Albery and J. R. Knowles in 1976. These enzymes catalyze biochemical reactions at high-speed. Their catalytic efficiency values range from 108-109 M-1s-1. These enzymes are also called 'diffusion-controlled' as the only rate-limiting step in the catalysis is that of the substrate diffusion into the active site. Examples include triose phosphate isomerase, fumarase, and superoxide dismutase.
Most enzymes...
Most enzymes...
3.8K
01:19Turnover Number and Catalytic Efficiency
9.8K
The turnover number of an enzyme is the maximum number of substrate molecules it can transform per unit time. Turnover numbers for most enzymes range from 1 to 1000 molecules per second. Catalase has the known highest turnover number, capable of converting up to 2.8×106 molecules of hydrogen peroxide into water and oxygen per second. Lysozyme has the lowest known turnover number of half a molecule per second.
Chymotrypsin is a pancreatic enzyme that breaks down proteins during digestion....
Chymotrypsin is a pancreatic enzyme that breaks down proteins during digestion....
9.8K
00:46Trophic Efficiency
20.2K
Trophic level transfer efficiency (TLTE) is a measure of the total energy transfer from one trophic level to the next. Due to extensive energy loss as metabolic heat, an average of only 10% of the original energy obtained is passed on to the next level. This pattern of energy loss severely limits the possible number of trophic levels in a food chain.
20.2K
01:30The Carnot Cycle
2.7K
Converting work to heat is an irreversible process, and the purpose of a heat engine is to reverse the effect partially. Heat engines aim to increase the efficiency of the reversal, that is, maximize the work retrieved from heat. If the efficiency of a heat engine were 100%, it would imply reversing the process completely without introducing any other effect. Thus, it would violate the second law of thermodynamics.
What could be the theoretical limit to the efficiency of a heat engine? The...
What could be the theoretical limit to the efficiency of a heat engine? The...
2.7K
01:10Column Efficiency: Plate Theory
432
Band broadening in a chromatography column is measured by its efficiency. This is determined by the number of theoretical plates (N). Theoretical plate theory states that a separation column consists of a continuous series of imaginary plates where solute equilibration occurs between stationary and mobile phases.
A higher number of theoretical plates signifies better column efficiency and improved separation capabilities. Plate height affects bandwidth and separation quality; it is inversely...
A higher number of theoretical plates signifies better column efficiency and improved separation capabilities. Plate height affects bandwidth and separation quality; it is inversely...
432
01:01Production Efficiency
16.7K
Net production efficiency (NPE) is the efficiency at which organisms assimilate energy into biomass for the next trophic level. Due to low metabolic rates and less energy spent on thermoregulatory processes, the NPE of ectotherms (cold-blooded animals) is 10 times higher than endotherms (warm-blooded animals).
16.7K