In utero nanoparticle delivery for site-specific genome editing
Adele S Ricciardi1,2,3, Raman Bahal1,2,4, James S Farrelly3
1Department of Biomedical Engineering, Yale University, New Haven, CT, 06511, USA.
Nature Communications
|June 28, 2018
Summary
This study shows safe fetal gene editing in mice using nanoparticles to correct a genetic defect causing beta-thalassemia. This approach offers a potential cure for monogenic disorders during pregnancy.
Area of Science:
- Genetics
- Biotechnology
- Developmental Biology
Background:
- Monogenic disorders cause significant infant and child mortality.
- Intrauterine gene editing offers potential for early intervention and cure.
Purpose of the Study:
- To demonstrate safe in utero gene editing for monogenic disorders.
- To correct a mutation in a mouse model of human beta-thalassemia.
Main Methods:
- Safe intravenous and intra-amniotic administration of polymeric nanoparticles to fetal mice.
- Nanoparticles delivered peptide nucleic acids (PNAs) and donor DNAs to correct the beta-globin gene mutation.
Main Results:
- Successful correction of the beta-thalassemia mutation in fetal mice.
- Sustained normal hemoglobin levels, reduced reticulocyte counts, and reversed splenomegaly postnatally.
- No detected off-target mutations, indicating safety.
Conclusions:
- Polymeric nanoparticles enable safe and effective fetal gene editing in vivo.
- This method holds promise for treating human monogenic disorders during pregnancy.
Related Concept Videos
01:28CRISPR/Cas9 Genome Editing
1.9K
The CRISPR-Cas system serves as a bacterial defense mechanism against invading genetic elements such as viruses and plasmids, forming the foundation for its adaptation as a powerful genome-editing tool. Originally discovered in prokaryotes, this system has been repurposed to revolutionize genetic engineering across a wide range of organisms, including plants, animals, and humans. The core component, Cas9, is an endonuclease derived from Streptococcus pyogenes, capable of introducing...
1.9K
02:23RNA Editing
9.9K
RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
9.9K
02:02Genomics
40.8K
Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
40.8K
02:30Genomic Imprinting and Inheritance
37.2K
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
37.2K
03:21Genome Size and the Evolution of New Genes
9.2K
While every living organism has a genome of some kind (be it RNA, or DNA), there is considerable variation in the sizes of these blueprints. One major factor that impacts genome size is whether the organism is prokaryotic or eukaryotic. In prokaryotes, the genome contains little to no non-coding sequence, such that genes are tightly clustered in groups or operons sequentially along the chromosome. Conversely, the genes in eukaryotes are punctuated by long stretches of non-coding sequence.
9.2K
02:16Comparing Mitochondrial, Chloroplast, and Prokaryotic Genomes
16.5K
The present-day mitochondrial and chloroplast genomes have retained some of the characteristics of their ancestral prokaryotes and also have acquired new attributes during their evolution within eukaryotic cells. Like prokaryotic genomes, mitochondrial and chloroplast genomes neither bind with histone-like proteins nor show complex packaging into chromosome-like structures, as observed in eukaryotes. Unlike mitotic cell divisions observed in eukaryotic cells, mitochondria and chloroplasts...
16.5K