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Triple vectors expand AAV transfer capacity in the retina

ABSTRACT: Triple vectors expand AAV transfer capacity in the retina

PROVIDER: PRJNA419212 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6310090_1.fastq.gz	Fastqsanger.gz
	SRR6310090_2.fastq.gz	Fastqsanger.gz
	SRR6310091_1.fastq.gz	Fastqsanger.gz
	SRR6310091_2.fastq.gz	Fastqsanger.gz
	SRR6310092_1.fastq.gz	Fastqsanger.gz

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Triple vectors expand AAV transfer capacity in the retina

Project description:Maddalena et al. showed that the limited DNA transfer capacity (~4.7kb) of adeno associated viral (AAV) vectors can be expanded up to 14kb with triple AAV vectors for the efficient expression of the therapeutic CDH23 (10.1kb) and ALMS1 (12.5kb) genes.

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Triple Vectors Expand AAV Transfer Capacity in the Retina.

Project description:Retinal gene transfer with adeno-associated viral (AAV) vectors holds great promise for the treatment of inherited retinal degenerations (IRDs). One limit of AAV is its transfer capacity of about 5 kb, which can be expanded to about 9 kb, using dual AAV vectors. This strategy would still not suffice for treatment of IRDs such as Usher syndrome type 1D or Alström syndrome type I (ALMS) due to mutations in CDH23 or ALMS1, respectively. To overcome this limitation, we generated triple AAV vectors, with a maximal transfer capacity of about 14 kb. Transcriptomic analysis following triple AAV transduction showed the expected full-length products along a number of aberrant transcripts. However, only the full-length transcripts are efficiently translated in vivo. We additionally showed that approximately 4% of mouse photoreceptors are transduced by triple AAV vectors and showed correct localization of recombinant ALMS1. The low-photoreceptor transduction levels might justify the modest and transient improvement we observe in the retina of a mouse model of ALMS. However, the levels of transduction mediated by triple AAV vectors in pig retina reached 40% of those observed with single vectors, and this bodes well for further improving the efficiency of triple AAV vectors in the retina.

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