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. 2023 Apr 24;15(5):1329. doi: 10.3390/pharmaceutics15051329

Table 1.

Benefits and drawbacks of different DNA donor template delivery platforms.

Delivery Platform Benefits Drawbacks
Non-viral delivery of naked DNA
  • Limited DNA damage response (DDR) and/or immune response

  • ssODNs can only deliver relatively short sequences, thus cannot mediate gene correction via introducing a normal copy of cDNA or replacing large segments of the gene (ssDNA with Cas9 target sites could allow for introduction of larger donor sequences)

  • Relatively simple to synthesize

  • Cannot always enable reporter gene cassettes

  • Degraded quickly upon entry to cells

AdV
  • Superior carrying capacity (~35 kb)

  • Reduced HDR efficiency

  • Markedly reduced extent of HDR-independent insertion into the genome due to the capped ends

AAV
  • Show the highest HDR efficiencies among the currently known vectors.

  • Triggers a DDR proportional to the MOI used

  • Limited carrying capacity (~4.8 kb)

  • Can lead to unwanted off-target donor integration

IDLV
  • Show marked HDR efficiency

  • Have not been widely applied or accepted yet; and follow-up studies are being conducted to elucidate the potential benefits

  • Relatively large carrying capacity (~10 kb)

  • Triggers a smaller DDR than AAV vectors

  • Less unwanted off-target integration