Home Cell Biology Molecular Cloning explained for Beginners
Steps
  1. 1 Prepare the vector backbone 00:20
  2. 2 Cut vector and insert with restriction enzymes 01:27
  3. 3 Purify DNA fragments by gel electrophoresis 02:36
  4. 4 Assemble recombinant DNA with ligase 03:50
  5. 5 Transform bacteria with recombinant DNA 04:36
  6. 6 Select transformed cells using antibiotics 05:15
  7. 7 Verify clone integrity by sequencing 05:30
Cell Biology YouTube (Curated Tutorials)

Molecular Cloning explained for Beginners

Protocol
Difficulty
intermediate

Steps

1
Prepare the vector backbone

Identify and prepare the vector DNA (typically a plasmid) containing essential elements like antibiotic resistance genes, origin of replication, promoter regions, and restriction sites where the insert will be cloned.

▶ 00:20
2
Cut vector and insert with restriction enzymes

Use restriction enzymes (molecular scissors) to cleave both the vector backbone and the prepared insert DNA at matching restriction sites, generating compatible sticky ends for assembly.

▶ 01:27
3
Purify DNA fragments by gel electrophoresis

Run the digested DNA samples through an agarose gel matrix under voltage to separate fragments by size, then extract and isolate the desired vector and insert bands from the gel.

▶ 02:36
4
Assemble recombinant DNA with ligase

Incubate the purified vector and insert together with DNA ligase enzyme to join the complementary sticky ends, creating recombinant DNA molecules.

▶ 03:50
5
Transform bacteria with recombinant DNA

Introduce the recombinant DNA into competent bacterial cells (e.g., E. coli) where the plasmids will be taken up and replicated to produce multiple copies of the cloned DNA.

▶ 04:36
6
Select transformed cells using antibiotics

Grow bacteria on antibiotic-containing media to identify and isolate only the cells that have successfully taken up the recombinant DNA, as they carry the antibiotic resistance gene.

▶ 05:15
7
Verify clone integrity by sequencing

Confirm successful cloning by performing PCR and DNA sequencing on the isolated clones to verify that the desired DNA fragment is present and correctly assembled.

▶ 05:30

🚨 Failure Case Library (2) + Submit your own case

critical
Confirmed colony later shows recombination or deletion
Initial screening looked correct, but on re-verification the insert is missing pieces or the vector has rearranged.
💡 4 · ✓ 4
severe
Subcloning Failure with Restriction Site Primers
Very few or no colonies obtained when subcloning PCR products generated with primers containing restriction enzyme sites, despite successful amplification
💡 4 · ✓ 5
💬 Comments coming soon